Preventol

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- Preservatives

Preventol

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CMK

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(cancels previous editions)

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Preventol

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CMK

Summary of Toxicity and Ecotoxicity

Active ingredient: 4-chloro-3-methylphenol; p-chloro-m-cresol

Synonyms: PCMC, CMK CAS No.: 59-50-7 Structural formula: OH CH₃ Cl

Index

A. Toxicity

B. Ecotoxicity

C. Evaluation

The following information is intended only for guidance. It contains a representative selection of the available data on: - toxicity and

- ecotoxicity of the product.

Citation of these compiled data for any purposes including product registrations is not permitted unless having obtained written permission by LANXESS. The information has been compiled from LANXESS's own studies, from sources available to the public and from data supplied by third parties. It does not claim to be exhaustive and does not release the user from the responsibility of carrying out his own tests where necessary. The information is rather intended as a guide to the procedures which should be followed during processing and use of the product to protect individuals and the environment. Any liability from our side is excluded.

For further questions please contact:

LANXESS Deutschland GmbH e-mail: [email protected]

D-50569 Köln website: http://www.lanxess.com

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A. Toxicity

1. Acute Studies

1.1 LD 50 oral : 3636 mg/kg, female rat MOBAY REPORT No. 146, 06.01.1981

1.2 LD 50 oral : 5129 mg/kg, male rat MOBAY REPORT No. 146, 06.01.1981

1.3 LD 50 oral : 1830 mg/kg, rat BAYER REPORT 21.04.1978

1.4 LD 50 percutaneous : > 2000 mg/kg, rat BAYER REPORT No. 17063, 18.08.1988

1.5 LD 50 percutaneous : > 5000 mg/kg, rabbit HAZLETON REPORT No. 339-108, 12.10.1979

1.6 In the inhalation hazard assessment air saturated with Preventol CMK at room temperature does not cause any symptoms in rats exposed with their whole body.

Exposure to air enriched with Preventol CMK in dust form by dynamic dust generation at a concentration of 704 mg/m³ air caused transitory irritating effects on the mucosa of the eyes and the inhalatory tract.

BAYER REPORT 10282, 21.10.1981.

1.7 Skin (rabbit):

no irritation (1 h exposure)

BAYER AG, Inst. of Toxicology, Feb. 2, 1991 strong irritation, corrosive effects (24 h exposure) BAYER REPORTS 20.09.1978 and 11.01.1983

1.8 Eyes (rabbit): strong irritation, clouding of cornea BAYER REPORTS 20.09.1978 and 11.01.1983

1.9 Sensitization:

By means of the maximization test according to MAGNUSSON-KLIGMAN, using 1 % induction concentration by intradermal injection, the consecutive challenge by topical application caused sensitization in guinea pigs in a low degree.

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By means of the open epicutaneous test according to KLECAK, using induction concentrations of 1-3-10-30 % and challenge concentrations of 3-10-30-100 %, no indication of sensitizing effects could be found on the skin of female guinea pigs.

BAYER REPORT 9447, 25.09.1980

In a patch-test according to the procedure of DRAIZE, using induction concentrations of 5-10-20 % and a challenge concentration of 5 % none out of 98, 88 or 66 human subjects was sensitized.

Repetition of the procedure with 5 % induction solution in petrolatum and 5 % challenge solution gave no sensitization in 31 humans.

MARZULLI, F.N.; MAIBACH, H.I.; Food Cosmet. Toxicology 12(1974)219-227

2. Subacute Studies

2.1 Wistar rats were treated for 28 consecutive days with Preventol CMK in doses of 0-2500-5000-10000 mg/kg in feed. Body weight gain was reduced in male rats at 10000 mg Preventol CMK/kg feed. No-effect level: 5000 mg/kg in the feed.

BAYER REPORT 17739, 20.02.1989

2.2 24-Day dermal study in rabbits using dosages of 0-10-40-160 mg/kg/d; no-effect level 160 mg/kg/d for systemic effects, i.e. no poisoning findings, as to mortality and moribundity, however treatment related dermal irritation findings already in the low-dose group.

BAYER REPORT 109, 31.07.1980

3. Subchronic Studies

Wistar rats were administered Preventol CMK for three months at the following concentrations in their diet: 0-150-500-1500 mg/kg/d. The 150 mg/kg/d dose was tolerated without any effects by males, as were the doses up to and including

500 mg/kg/d by the females.

BAYER REPORT 17414, 24.11.1988

4. Chronic / Oncogenicity Studies

Wistar rats were administered 4-chloro-3-methylphenol in doses of 0-400-2000-10000 ppm in feed for 53 and 104 weeks. Up to 2000 ppm no substance-related increased incidences of clinical signs were noted (NOEL 2000 ppm). In the highest dose group a reduced body weight gain was observed for both sexes. In male rats which were treated with 10000 ppm damage of the kidneys was noted. There were no signs of toxicity to other organs or of cancerogenic effects in all tested doses.

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5.1 4-Chloro-3-methylphenol was tested in the Salmonella/microsome test with the Salmonella typhimurium strains TA 98, TA 100, TA 1535 and TA 1537. Neither without nor with metabolic activation (S-9 mix) mutagenic effects could be observed.

BAYER REPORT No. 20516, 08.08.1991

5.2 In the Chinese hamster ovary cell/hypoxanthine-guanine-phosphoribosyltransferase (CHO-HGPRT) test no mutagenic effects were detected with Preventol CMK. BAYER REPORT 17755, 22.02.1989

5.3 In the rat primary hepatocyte unscheduled DNA synthesis (UDS) test no mutagenic effects were detected.

HAZLETON REPORT R4545, 04.10.1988

5.4 In the micronucleus test in vivo in mice on the chromosomes of the erythroblastes of the bone marrow no mutagenic effects were detected with Preventol CMK.

BAYER REPORT 18686, 17.01.1990

6. Teratogenicity

Preventol CMK was tested in pregnant Wistar rats in doses of 0-30-100-300 mg/kg. Maternal toxic effects were detected in the 100 and 300 mg/kg dose groups. The NOEL for the fetal development was 100 mg/kg.

BAYER REPORT No. 20869, Nov. 29, 1991

7. Biokinetics

7.1 The excretion of 4-chloro-3-methylphenol, following a single oral application of 300 mg/kg, occurs via the renal way mainly within 24 hours; the median value for unchanged compound is 67.2 %; noticable concentrations in the excrements were found only within 24 hours with a median value of 0.4 % of the applied dosage; because of the rapid and practically complete excretion, accumulation in fat and liver is unlikely.

BAYER REPORT 9605, 02.12.1980

7.2 After 1, 4, 8 and 13 weeks of a 13-week feeding test in rats using dosages of 0-150-500-1500 mg/kg/d, animals were sacrificed; liver and fat were analysed for 4-chloro-3-methylphenol; no accumulation was found.

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B. Ecotoxicity

1. Biodegradation

1.1 Under the condition of the Closed Bottle Test (OECD 301 D) and working with adapted media, there is found, relative to a "chemical oxygen demand" (COD) of 1730 mg/L, a "biological oxygen demand" (BOD) of 60-70 % (5 days), 80-85 % (10 days) and 85-90 % (20 days).

BAYER REPORT 26.05.1981

1.2 In the OECD-Confirmatory Test (organic medium test) there is complete biodegradation of PCMC in the presence of activated sludge, when starting with concentrations of 20 mg/L PCMC and an adaption period of 3 weeks.

VOETS J.P. et al.; J. Appl. Bacteriol. 40(1976)67-72

1.3 Under the conditions of the Modified MITI-I Test (OECD 301 C) there is observed more than 90 % biodegradation by mineralisation, documented by the formation of stoichiometric amounts of chloride ions.

1.4 In concentrations up to 100 mg/L natural bacteria in Rhine River water are capable to mineralize PCMC completely within 7-14 days when the substance is offered as sole carbon source. The degradation can be monitored by measurement of the formation of chlorid ions liberated from PCMC.

BAYER REPORTS 14/76 and 11/76

2. Toxicity to Fish

2.1 Toxicity of 4-chloro-3-methylphenol to Leuciscus idus: LC 50 : 1.2 mg/L (48 h exp.)

2.2 Toxicity of 4-chloro-3-methylphenol to Pimephales promelas: LC 50 : 7.6 mg/L (96 h exp.)

HOLCOMBE, G.W. et al.; Environmental Pollution (Ser.A) 35(1984)367-381

2.3 Toxicity of 4-chloro-3-methyl phenol to Oncorhynchus mykiss: LC 50 : 0.917 mg/L (96 h exp.)

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- 7 - 3. Toxicity to Bacteria

4-Chloro-3-methylphenol was tested in the respiration inhibition test with activated sludge (OECD 209).

EC 50 : 60 mg/L BAYER REPORT 18.02.1988

4. Toxicity to Daphnia

4.1 The acute toxicity of 4-chloro-3-methylphenol was investigated in Daphnia magna under static conditions according to EPA/FIFRA Guideline 72-2.

EC 50 (48 h) : 2.29 mg/L LC 50 (48 h) : 3.90 mg/L NOEC (48 h): 1.73 mg/L

MILES REPORT No. 105021, Feb. 19, 1993

4.2 4-Chloro-3-methylphenol was tested for chronic toxicity to Daphnia magna. 21-Day reproduction toxicity:

NOEC : 1.3 mg/L

KÜHN, R. et al.; RESEARCH REPORT 10603052, Inst. Wasser-, Boden- und Lufthygiene des BGA, Berlin, March 1988

5. Toxicity to Algae

4-Chloro-3-methylphenol was tested for toxicity in a Growth inhibition test with Scenedesmus subspicatus CHODAT

EC 10 (48 h) : 5.7 mg/L EC 50 (48 h) : > 10 mg/L EC 10 (72 h) : 4.7 mg/L EC 50 (72 h) : > 10 mg/L EC 10 (96 h) : 5.2 mg/L EC 50 (96 h) : > 10 mg/L KÜHN, R. et al.; Wat. Res. 24(1990)31-38

6. Bioaccumulation

The bioaccumulation of 4-chloro-3-methylphenol was investigated according to test guideline OECD 305 C in Oryzae latipes in a 6 week test. A BCF of 10 was found.

OECD Progress Reports From Clearing Houses For Specific Chemicals 1990; Room Document for the 15th Joint Meeting of the Chemicals Group and Management Commitee, drafted 26th Oct. 1990, Paris

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C. Evaluation

Citation taken from the assessment of the experts of the German Senate Commission for Testing of Harmful Chemicals:

 Under the usual conditions of the working place the danger for sensitizing humans, when handling material with use-concentrations of max. 0.5 % PCMC, is low. At higher concentrations irritation of skin and after prolonged exposure inflammation and other harm to skin may occur, based on results obtained from animal testings. An increased adsorption via skin is not to be expected.

 The contact of PCMC in form of fumes or dust with the eyes may lead to irritation of the iris and the conjunctiva, under certain conditions also to clouding of the cornea, so corresponding protective measurements are recommended.

 There are no indications for systemic effects of PCMC in the human organism. Due to results of tests in animals the rapid metabolism of PCMC should pose no danger to man when handling formulations containing up to 0.5 % PCMC as use concentration.

 For the establishment of a MAK-value neither the observations in man nor in animal testings are sufficient.