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Toxicological information

Acute Toxicity: dermal

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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Read-across fromsupporting substance. Guideline study to GLP.
Justification for type of information:
See attached justification document
Cross-reference
Reason / purpose:
read-across: supporting information
Reference
Endpoint:
acute toxicity: dermal
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Justification for type of information:
See attached justification document
Reason / purpose:
read-across source
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1996
Report Date:
1996

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Principles of method if other than guideline:
Not applicable.
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
other: Liquid.

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Zeneca Pharmaceuticals, Alderley Park, Macclesfield, Cheshire UK
- Age at study initiation: young adults
- Weight at study initiation: 273-299 g(m) 206-226 (f)
- Fasting period before study: not applicable
- Housing: individually
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 +/- 2
- Humidity (%): 55 +/- 15
- Air changes (per hr): 25-30
- Photoperiod (hrs dark / hrs light): 12:12

IN-LIFE DATES: from 14 November 1995 to 28 November 1995

Administration / exposure

Type of coverage:
occlusive
Vehicle:
water
Details on dermal exposure:
TEST SITE
- Area of exposure: 7cm x 7cm
- % coverage: not stated
- Type of wrap if used: gauze patch covered by plastic film

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, washed with water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 14-16 mg/cm2 (males); 11-12 mg/cm2 (females)
- Concentration (if solution): 300 mg/ml
- Constant volume or concentration used: yes

VEHICLE
- Amount(s) applied (volume or weight with unit): water, to give dilution to 300 mg/ml test substance
Duration of exposure:
24 h
Doses:
2000 mg/kg
No. of animals per sex per dose:
5
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: once between 1 and 4 hours post-application, then daily
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs including local effects, body weight

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
Male: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Female: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Clinical signs:
Signs of toxicity related to dose levels:
No deaths occurred and no signs of systemic toxicity were
observed.
Gross pathology:
Effects on organs:
No treatment-related macroscopic findings were observed.
Other findings:
Signs of toxicity (local):
Slight to moderate irritation was observed in all the animals. Signs of necrosis were observed in two males and in one female. There was clear evidence of recovery and repair in these animals at the end of the observation period.

The test sample stained the application sites yellow but this did not prevent the accurate clinical assessment of erythema.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The acute dermal LD50 is greater than 2000 mg/kg. ITC 826 Concentrate is not classified for acute dermal toxicity.
Executive summary:

A sample of ITC 826 Concentrate was assessed for its acute dermal toxicity. A group of five male and five female rats received a single dermal application of 2000 mg/kg (corrected for water content) of the test sample. The animals were assessed daily for any signs of systemic toxicity and dermal irritation and their bodyweights were recorded at intervals throughout the study. At the end of the study, the animals were killed and subjected to a macroscopic post mortem examination.

None of the animals died and there were no significant signs of systemic toxicity. Moderate irritation was observed in both males and females. The acute dermal median lethal dose of the test sample is in excess of 2000 mg/kg for male and female rats.