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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
Study period:
June 25, 1992 - July 9, 1992
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Study conducted in accordance with OECD 402 and GLP. There is 1 deviation: during the 14 days observation period, the animals were not caged individually but by sex. But it is assumed that this deviation does not significantly influence the reliability of the study. Batch number and purity not given.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1992
Report Date:
1992

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
; during the 14 days observation period, the animals were not caged individually but by sex
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): XDI: 1,3-Benzenebis(methylisocyanate)
- Appearance: clear colourless liquid
- Specific gravity (determined before the study): 1.188

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK) Ltd., Manston, Kent, UK
- Age at study initiation: approximately 10 to 14 weeks old
- Weight at study initiation:
Males: 244 - 265 g
Females: 202 - 243 g
- Fasting period before study: not applicable
- Housing:
The animals were housed in suspended polypropylene cages furnished with softwood sawdust. The animals were housed individually during the 24-hour exposure period and in groups of 5, by sex, for the remainder of the study
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: minimum period of 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 23 °C
- Humidity (%): 47 - 75% (on 2 occasions >70%)
- Air changes (per hr): 15 per hr
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: an area equivalent to 10% of the total body surface ( 5 cm x 4 cm)
- Type of wrap if used: surgical gauze semi-occluded with a piece of self-adhesive bandage (HYPERTIE), the bandage was further secured with a piece of BLENDERM wrapped around each end

REMOVAL OF TEST SUBSTANCE
- Washing (if done): residual material was removed by wiping with cotton wool moistened with arachis oil
- Time after start of exposure: 24 hr

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw = 1.69 mL/kg bw
- Concentration (if solution): undiluted

VEHICLE
Not applicable
Duration of exposure:
24 h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5 males and 5 females
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Deaths and overt signs of toxicity were recorded 0.5; 1; 2 and 4 hours after dosing and subsequently once daily for 14 days
Individual bodyweights were recorded prior to treatment on day 0 and on days 7 and 14
- Necropsy of survivors performed: yes
- Other examinations performed: dermal reactions were also recorded
Statistics:
Not applicable

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No deaths
Clinical signs:
- No signs of systemic toxicity were noted
- Adverse skin reactions were noted at the treatment site of all animals from day 5 onwards
These reactions included:
*well-defined erythema and oedema
*light brown discolouration
*small superficial scattered scabs
*keratolysis (glossy skin)
*dried blood
*crust formation
*scabbing lifting to reveal glossy skin hardened dark brown scab and desquamation
Body weight:
One female showed a slight loss in bodyweight during the 1st week. All other animals showed gains in bodyweight over the study period.
Gross pathology:
No abnormalities were noted

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In an acute dermal toxicity study conducted in accordance with OECD 402 and GLP (limit test), a LD50 of >2000 mg/kg bw was found. No deaths occurred.
Executive summary:

In an acute dermal toxicity study, conducted in accordance with OECD 402 and GLP (limit test), 5 female and 5 male rats were semi-occlusively exposed for 24 hours to the undiluted test substance at a dose of 2000 mg/kg bw. No apparent systemic toxicity was seen and no deaths occurred. Dermal reactions were noted, starting from day 5 onwards. The conducted gross pathology did not detect any abnormalities.