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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Taken from EU Risk Assessment Report - Reviewed by the Danish Environmental Protection Agency. Guideline Study.

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
2002

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
not specified
Test type:
standard acute method

Test material

Constituent 1
Chemical structure
Reference substance name:
4-chloro-o-cresol
EC Number:
216-381-3
EC Name:
4-chloro-o-cresol
Cas Number:
1570-64-5
Molecular formula:
C7H7ClO
IUPAC Name:
4-chloro-2-methylphenol

Test animals

Species:
rat
Strain:
not specified
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Housing: Individually caged.
- Diet (e.g. ad libitum): conventional laboratory diet
- Water (e.g. ad libitum): Unlimited supply
- Acclimation period: at least 5 days prior to the test

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20°C +/- 3°C
- Humidity (%): 30-70%
- Air changes (per hr): Not specified
- Photoperiod (hrs dark / hrs light): 12 hours light/12 hours dark

Administration / exposure

Type of coverage:
occlusive
Vehicle:
other: arachidis oil
Details on dermal exposure:
TEST SITE
- Area of exposure: Dorsal area of the trunk
- % coverage: approximately 10% of the total body suface area

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Residual test material removed by washing with water or a suitable solvent 24 hours after dosing.
- Time after start of exposure: 24hours
Duration of exposure:
24 hours
Doses:
The doses tested were as follows:
1,667, 2,000, 2,400 and 2,880 mg PCOC
No. of animals per sex per dose:
There were 5 male and 5 female rats per dose
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
ca. 2 240 mg/kg bw
Remarks on result:
other: Range 2023 -2484 mg/kg/bw
Mortality:
See table below (Table 1) for mortality details
Clinical signs:
During the first 24 hours after treatment blood was observed in the urine of all the rats. The day after treatment erythema and oedema were observed at the application sites. Paresis occurred in nearly all the animals 1-6 hours after treatment.
Depressions occurred up to 2 days after treatment and ruffled fur up to 3 days after treatment.
Gross pathology:
At necropsy, bleeding of the lungs, a mucous, red-yellow content of the jejunum (intestine), enlarged kidneys and blood or blood coagulum in the bladder and bleeding of the bladder walls were all observed.
In animals sacrificed on day 14, weak bleeding of the intestine was observed in five of the rats, the dose levels were not stated.

Any other information on results incl. tables

Table 1. Summary of mortality rates.

 Dose Level, mg/kg bw  Mortality (out of 10)  Time Period
 1667  0/10  -
 2000  4/10  within 1 day of dosing
 2400  6/10  within 1 day of dosing
 2880  9/10  within 6 hours of dosing

                                  

Applicant's summary and conclusion

Interpretation of results:
other: Not classified as harmful in contact with skin
Remarks:
Criteria used for interpretation of results: other: Approved Classification and Labelling Guide (Sixth Edition), Chemicals (Hazard Information and Packaging for Supply) Regulations 2009 (CHIP 4)
Conclusions:
Based on the results obtained in this study, 4-chloro-o-cresol is not classified as harmful in contact with skin.
Executive summary:

 A guideline study was performed on groups of five male and five female rats at dose levels ranging from 1667 - 2880 mg/kg bw.

In the 2880 mg/kg dose group 9 animals died within 6 hours of dosing, in the 2400 mg/kg dose group 6 animals died within 1 day of dosing, in the 2000 mg/kg dose group 4 animals died within 1 day of dosing, no animals died in the 1667 mg/kg dose group.

At necropsy bleeding of the lungs, a mucous, red-yellow content of the jejunum (intestine), enlarged kidneys and blood or blood coagulum in the bladder and bleeding of the bladder walls were all observed.

In animals sacrificed on day 14, weak bleeding of the intestine was observed in five of the rats; the dose levels were not stated.

During the first 24 hours after treatment blood was observed in the urine of all the rats. The day after treatment erythema and oedema were observed at the application sites. Paresis occurred in nearly all the animals 1-6 hours after treatment. Depressions occurred up to 2 days after treatment and ruffled fur up to 3 days after treatment. The LD50 was derived to be 2240 mg/kg/bw.