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Toxicological information

Repeated dose toxicity: dermal

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Administrative data

Endpoint:
short-term repeated dose toxicity: dermal
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
Not applicable
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: 2a: Reliable with restrictions; acceptable, well- documented study report which meets basic scientific principles
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1985

Materials and methods

Principles of method if other than guideline:
Other - Not listed
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Polyethylbenzene (PEB) Bottoms (CAS No. 6897-43-9)
- Analytical purity: not stated

Test animals

Species:
rat
Strain:
Fischer 344
Sex:
male/female
Details on test animals and environmental conditions:
At the start of the experiment, animals were 70 days of age and weighed between 129.27 g to 206.32 g. During the study, animal rooms were maintained at an average ambient temperature of 73.6ºF and relative humidity of 55.5%.

Administration / exposure

Type of coverage:
not specified
Vehicle:
paraffin oil
Details on exposure:
Prior to treatment initiation, the backs of all animals were clipped free of hair. Each animal was fitted with an Elizabethan collar to prevent ingestion of test or control substances. The three dose groups consisted of: vehicle control (light paraffin oil) [Group I], diluted low-dose (50%) PEB Bottoms [Group II], high dose (100%) PEB Bottoms [Group III]. The appropriate doses or test control substance were applied topically to the prepared back of 5 test animals per group for a period of 6 hours. Treatment was performed once daily for a total of 5 doses.
Duration of treatment / exposure:
Five days
Frequency of treatment:
Daily
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 1 and 2 g/kg bw
Basis:
nominal per unit body weight
No. of animals per sex per dose:
Five
Control animals:
yes, concurrent vehicle

Examinations

Observations and examinations performed and frequency:
Animals were observed daily for clinical signs, mortality and moribundity. Dermal reactions were observed and scored twice on the initial dosing day and at the time of residual test substance removal. The Draize Scoring System for evaluating dermal reactions was used for scoring purposes.

Body weights were recorded immediately prior to initial treatment and again at necropsy.
Sacrifice and pathology:
All animals surviving to the scheduled study termination were sacrificed on Day 8 and gross necropsies on all animals were performed.
Other examinations:
Not applicable
Statistics:
Mean and standard deviation

Results and discussion

Results of examinations

Clinical signs:
effects observed, treatment-related
Mortality:
mortality observed, treatment-related
Body weight and weight changes:
effects observed, treatment-related
Food consumption and compound intake (if feeding study):
not examined
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not specified
Haematological findings:
not examined
Clinical biochemistry findings:
not examined
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
Organ weight findings including organ / body weight ratios:
not examined
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
not examined
Histopathological findings: neoplastic:
not examined
Details on results:
All animals survived to the termination of the study. No mortality occurred as a result of the 5-day repeated dermal application of Polyethylbenzene Bottoms to male and female rats at dose levels of 1.0 g/kg (Group II) and 2.0 g/kg (Group III). Statistical analyses of group mean body weights revealed weight losses among males and females at both the 1.0 and 2.0 g/kg dose levels that were significant at the 99% confidence level.

A yellow brown discoloration of the test site was seen among all animals treated with the test substance. Dermal irritation was observed among animals in Groups II and III. Barely perceptible erythema was observed in the Group II (1.0 g/kg) animals. Erythema (ranging from very slight to well defined) and barely perceptible edema were seen among animals in Group III (2.0 g/kg).

Focal thickening of the skin at the point of application of the test substance was observed in Group III (2.0 g/kg).

Effect levels

Dose descriptor:
LOEL
Effect level:
1 000 mg/kg bw/day
Sex:
male/female
Basis for effect level:
other: Based on Local skin irritation at the sight of application and bodyweight differences

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

Not applicable

Applicant's summary and conclusion

Conclusions:
Dermal exposure to the test material for 5 daily doses produced signs if skin irritation and also a decrease in bodyweight gain. Due to these effects occuring at both dose levels it is not possible to assign a NOEL. However the effects observed are likely the result of toxicity to the site of dosing rather than systemic toxicity.