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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:
No data
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to a test protocol that is comparable to the appropriate OECD test guideline. It was not compliant with GLP.

Data source

Reference
Reference Type:
secondary source
Title:
Unnamed
Year:
1981

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
no
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): Hexamethyldisilazane; Organofunctional Silane A-166; 1,1,1,3,3,3-hexamethyldisilazane.


No further details available

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: No data
- Age at study initiation: No data
- Weight at study initiation: 2-3 Kg
- Fasting period before study: No data
- Housing:No data
- Diet (e.g. ad libitum): No data
- Water (e.g. ad libitum): No data
- Acclimation period: No data


ENVIRONMENTAL CONDITIONS
- Temperature (°C): No data
- Humidity (%): No data
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): No data


IN-LIFE DATES: No data

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: No data
- % coverage: No data
- Type of wrap if used: Impervious sheet


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


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): Males: 1.0, 0.71 and 0.5 ml/kg bw; females: 16.0, 4.0, 1.0, 0.5 and 0.25 ml/kg bw
- Concentration (if solution): Undiluted
- Constant volume or concentration used: yes
Duration of exposure:
24 hours
Doses:
1.0, 0.71, and 0.50 mL/kg bw (774, 550, and 387 mg/kg bw based on a density of 0.774 g/ml) in males and 16.0, 4.0, 1.0, 0.5, and 0.25 mL/kg bw (12,384, 3096, 774, 387, 194 mg/kg bw based on a density of 0.774 mg/kg bw) in females
No. of animals per sex per dose:
Four (except 16 and 4 ml/kg bw levels used two females each)
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations were made daily. Weights were measured before dosing and on Days 7 and 14.
- Necropsy of survivors performed: yes
Statistics:
LD50s were calculated using the 'moving average method'.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
547 - 589 mg/kg bw
Mortality:
Males: 4/4, 1/4 and 0/4 at 1.0, 0.71 and 0.5 ml/kg bw, respectively.
Females: 2/2, 2/2, 4/4, 0/4 and 0/4 at 16.0, 4.0, 1.0, 0.5 and 0.25 ml/kg bw, respectively.
Clinical signs:
See Table 1
Body weight:
It is not clear whether differences are statistically significant, but the losses are obviously a result of treatment. IULCID 2008 reported the following:
Males: 0.71 ml/kg bw: Weight change (g) at 7 days: -172 to 19 (mean -92); Weight change (g) at 14 days: 185 to 243 (mean 205)
Males: 0.5 ml/kg bw: Weight change (g) at 7 days: -246 to 20 (mean -58); Weight change (g) at 14 days: -249 to 225 (mean 21)
Females: 0.5 ml/kg bw: Weight change (g) at 7 days: -99 to 18 (mean -66); Weight change (g) at 14 days: -38 to 355 (mean 96)
Females: 0.25 ml/kg bw: Weight change (g) at 7 days: 47 to 107 (mean 73); Weight change (g) at 14 days: -68 to 306 (mean 149)
Gross pathology:
See Table 1
Other findings:
See table 1

Any other information on results incl. tables

Table 1 Summary of mortality, clinical and necropsy findings.

 Group (ml/kg bw)  Number of deaths/total exposed  Time to death (d)  Clinical observations  Necropsy findings
 Males            
 0.5  0/4  -  Sluggishness on Days 1 and 2 (2/4), skin erythema, edema, necrosis on Day 1 and desquamation by Day 14.  Trachea red (1/4), liver with tan foci (coccodiae; 1/4)
 0.71  1/4  3 Prostration in one animal, skin erythema and necrosis, and scabs by Day 14.  Nothing remarkable
 1.0  4/4  1, 1, 2, 3 Prostration in two animals, skin erythema, edema and necrosis Lung & liver dark (1/4), trachea red (2/4), bladder distended filled with red/yellow liquid (1/4)
 Females            
 0.25  0/4  - Capillary injection, erythema, necrosis, spots of ecchymosis on Day 1, desquamation, scabs at 14 days.  Lungs mottled dark red (2/4) and trachea slight redness along mucous lining (1/4)
 0.5  0/4  -  Sluggishness on Day 1, skin erythma, edema and necrosis on Day 1 with desquamation and scabs by Day 14.  Lungs and trachea dark red (1/4)
 1.0  4/4  1, 1, 1, 3 Lethargy, slow and shallow breathing (1 hour), skin erythema and necrosis  Lungs mottled dark red (2/4) and trachea dark red (1/4)
 4.0  2/2  1, 1 Signs of discomfort, lethargy slow and shallow breathing (30 mins), skin erythema and necrosis  Lungs with dark red patches
 16.0  2/2  0, 0 (within 2 hours) Signs of discomfort, skin erythema and necrosis  Nothing remarkable


Applicant's summary and conclusion

Interpretation of results:
harmful
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In an acute dermal toxicity study (reliability score 2) conducted using a protocol that was comparable to OECD 402, but not to GLP, the LD50s for male and female rabbits were determined to be 0.761 (0.620 to 0.935) mL/kg bw (589 mg/kg bw) and 0.707 (0.463 to 1.08) mL/kg bw (547 mg/kg bw), respectively.
Executive summary:

In an acute dermal toxicity study (reliability score 2) conducted using a protocol that was comparable to OECD 402, but not to GLP, New Zealand white rabbits (two or four/sex/dose) were exposed to undiluted hexamethyldisilazane under an occlusive patch for 24 hours. The doses used were: 1.0, 0.71, and 0.50 ml/kg bw (774, 550, and 387 mg/kg bw based on a density of 0.774 g/ml) in males and 16.0, 4.0, 1.0, 0.5, and 0.25 m/kg bw (12,384, 3096, 774, 387, 194 mg/kg bw based on a density of 0.774 mg/kg bw) in females. After which, excess test substance was washed off the skin. The animals were then observed for 14 days for signs of toxicity and mortality. A necrospy examination was conducted on all animals. Body weights were recorded before the exposure and on Days 7 and 14 of the observation period. At doses of 1.0 ml/kg bw all animals died, and one male died at 0.71 ml/kg bw. There were no other deaths. All groups showed signs of severe skin irritation. Clinical signs were mainly sluggishness, prostration and lethargy which increased with increasing dose. There were effects on body weight gain but these did not appear to be dose-related. At necropsy there was trachea and lung redness in some groups, but the finding was sporadic across the whole dose range. It was concluded that the LD50 in this study was 547 -589 mg/kg bw.