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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: Although the study pre-dates current test guidelines and GLP regulations, the design follows standard methods for the determination of acute toxicity.

Data source

Reference
Reference Type:
grey literature
Title:
Unnamed
Year:
1977
Report Date:
1977

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
no
Remarks:
Study pre-dates implementation of GLP regulations
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): TK 10 524 - Nadic methyl anhydride (Hardener HY 906)

Test animals

Species:
rat
Strain:
other: Tif: RAIf
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: In-house breeding colony
- Age at study initiation: No data
- Weight at study initiation: 155 - 208 g
- Fasting period before study: Overnight
- Housing: Group caged (5 same sex / cage)
- Diet (e.g. ad libitum): Standard rodent diet pellets (Nafag Gossau SG), ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: Minimum of 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-23 deg C
- Humidity (%): 50-60%
- Photoperiod (hrs dark / hrs light): 10 hours dark / 14 hour light

IN-LIFE DATES: From: March 1977 To: May 1977

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: 100 cm2 / kg body weight
- Type of wrap if used: Occlusive dressing held in place by adhesive elastic bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Yes - warm water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000, 3000, 4000 and 5000 mg/kg body weight
- Constant concentration used: yes (undiluted)
Duration of exposure:
24 hours
Doses:
2000, 3000, 4000 and 5000 mg/kg body weight
No. of animals per sex per dose:
5 males / 5 females / dose
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: 24, 48 and 72 hours and 14 days after dosing; Body weights recorded at test start and termination
- Necropsy of survivors performed: yes
Statistics:
Probit analysis

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
4 920 mg/kg bw
Based on:
test mat.
95% CL:
3 670 - 6 590
Mortality:
2000 mg/kg - 0/5 males, 0/5 females
3000 mg/kg - 1/5 males, 1/5 females
4000 mg/kg - 2/5 males, 1/5 females
5000 mg/kg - 2/5 males, 3/5 females
Clinical signs:
2000 mg/kg - Reduced activity and ataxia seen after 60 minutes. After 3 hours palpebral closure apparent. After 6 hours ventricumbency occurred Palpebral closure and humpbacked posture lasted 2 days.
3000 mg/kg - Reduced activity and ataxia seen after 60 minutes. After 1-3 hours palpebral closure, ventricumbency, inhibition of pain response (pinching) apparent. Also, after 1 day, irregular breathing and humpbacked posture noted and, after 2 days, roughening of the coat. After 3 days no symptoms remained.
4000 mg/kg – Symptoms as above. Recovery of surviving animals after 4 days.
5000 mg/kg – Symptoms as above. Recovery of surviving animals after 3 days.
Body weight:
Body weight changes in surviving animals were not remarkable
Gross pathology:
2000 mg/kg - No gross organ changes seen
3000 mg/kg – Decedent animals not examined due to cannibalism by cage mates. No gross organ changes seen in surviving animals.
4000 mg/kg – Examination of decedent animals revealed congestion of the lungs, bloody stomach content and petechial haemorrhage on the stomach mucosa. Surviving animals showed no pathology.
5000 mg/kg – As above

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Acute toxicity has been determined in the rat following administration of a single dose to the skin for a 24 hour period. The median lethal dose (LD50) was determined to be 4920 mg/kg body weight.
Executive summary:

Acute toxicity has been determined in the rat following administration of a single dose to the skin for a 24 hour period. The median lethal dose (LD50) was determined to be 4920 mg/kg body weight.