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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:
1984
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Acceptable, well-documented study report equivalent or similar to OECD guideline : GLP
Justification for type of information:
A discussion and report on the read across strategy is given as an attachment in IUCLID Section 13.
Cross-reference
Reason / purpose for cross-reference:
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
Study period:
1984
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Acceptable, well-documented study report equivalent or similar to OECD guideline : GLP
Justification for type of information:
A discussion and report on the read across strategy is given as an attachment in IUCLID Section 13.
Reason / purpose for cross-reference:
read-across source
Sex:
male/female
Dose descriptor:
LD50
Effect level:
>= 3 160 mg/kg bw
Mortality:
none
Clinical signs:
There was an overall low incidence of clinical in-life observations noted during the study. Observations included nasal discharge, dry rales, alopecia. Topical exposure elicited very slight to well defined erythema in all animals and very slight edema in four animals. Desquamation was noted in five animals during the study. By Day 14, all animals were clear of erythema and edema
Body weight:
3/6 test animals gained weight during the 14 day test period.
Gross pathology:
N/A
Other findings:
N/A
Interpretation of results:
other: Not classified
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
The dermal LD50 for MRD-83-349 is greater than 3160 mg/kg. Classification as an acute dermal toxicant is not warranted under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP) or under Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.
Executive summary:

This data is being read across from the source study that tested Hydrocarbons, C9-C11, isoalkanes, cyclics, <2% aromatics based on analogue read across.

The acute dermal toxicity of MRD-83-349 was evaluated in rabbits following topical occlusive exposure.  Test material was applied as a single dose of 3160 mg/kg to the clipped backs of 3 male and 3 female rabbits, covered with a gauze patch, and secured with non-irritating tape and a plastic sleeve.  The test material remained in contact with the skin for 24 hours.  Observations were made as to the nature, onset, severity, and duration of toxicological signs 2, 4, and 24 hours after dosing and once per day thereafter, for a total of 14 days.  Dermal responses were evaluated 24 hours after topical application and on Days 3, 7, 10, and 14 according to the Draize method of scoring.  Application of MRD-83-349 at a dose level of 3160 mg/kg showed no evidence of systemic toxicity under the conditions of this study and all animals survived to study termination.  There were no deaths or treatment-related clinical signs.  Topical exposure elicited very slight to well defined erythema in all animals and very slight edema in four animals.  Desquamation was noted in five animals during the study.  By Day 14, all animals were clear of erythema and edema.  Based on the results of this study, the dermal LD50 for MRD-83-349 is greater than 3160 mg/kg. Classification as an acute dermal toxicant is not warranted under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP) or under Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1984
Report date:
1984

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
yes
Test type:
standard acute method

Test material

Constituent 1
Reference substance name:
Hydrocarbons, C9-C11, isoalkanes, cyclics, < 2% aromatics
EC Number:
926-952-5
IUPAC Name:
Hydrocarbons, C9-C11, isoalkanes, cyclics, < 2% aromatics
Details on test material:
- Name of test material (as cited in study report): MRD-83-349
- Physical state: clear colorless liquid
- Storage condition of test material: room temperature

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Hazleton
- Age at study initiation: 19 weeks
- Weight at study initiation: 3.14-3.51
- Housing: individual
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 50 days


ENVIRONMENTAL CONDITIONS
- Temperature (°F): 65-71
- Humidity (%): 40-70
- Photoperiod (hrs dark / hrs light): 12/12


Administration / exposure

Details on dermal exposure:
TEST SITE
- Area of exposure: shoulder region to lumbar region
- Type of wrap if used: gauze and plastic sleeve


REMOVAL OF TEST SUBSTANCE
- Washing (if done): no washing, wiped with gauze
- Time after start of exposure: 24h
Duration of exposure:
The test material was applied to the skin at the appropriate dose, covered with a gauze patch, secured with tape, and covered with a plastic sleeve. After ca. 24h of exposure, the plastic sleeve, tape and gauze patch were removed. The skin was then wiped (but not washed) with gauze and water to remove any remaining test material.
Doses:
The test material was applied to the skin at the appropriate dose, covered with a gauze patch, secured with tape, and covered with a plastic sleeve. After ca. 24h of exposure, the plastic sleeve, tape and gauze patch were removed. The skin was then wiped (but not washed) with gauze and water to remove any remaining test material.
No. of animals per sex per dose:
6 animals/dose (3 males; 3 females)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:2, 4, 24 hours after dosing and daily for 14 days
- Necropsy of survivors performed: no
- Other examinations performed: clinical signs, body weight
Statistics:
The means and standard deviations of the body weights were calculated.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
>= 3 160 mg/kg bw
Mortality:
none
Clinical signs:
There was an overall low incidence of clinical in-life observations noted during the study. Observations included nasal discharge, dry rales, alopecia. Topical exposure elicited very slight to well defined erythema in all animals and very slight edema in four animals. Desquamation was noted in five animals during the study. By Day 14, all animals were clear of erythema and edema
Body weight:
3/6 test animals gained weight during the 14 day test period.
Gross pathology:
N/A
Other findings:
N/A

Applicant's summary and conclusion

Interpretation of results:
other: Not classified
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
The dermal LD50 for MRD-83-349 is greater than 3160 mg/kg. Classification as an acute dermal toxicant is not warranted under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP) or under Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.
Executive summary:

The acute dermal toxicity of MRD-83-349 was evaluated in rabbits following topical occlusive exposure.  Test material was applied as a single dose of 3160 mg/kg to the clipped backs of 3 male and 3 female rabbits, covered with a gauze patch, and secured with non-irritating tape and a plastic sleeve.  The test material remained in contact with the skin for 24 hours.  Observations were made as to the nature, onset, severity, and duration of toxicological signs 2, 4, and 24 hours after dosing and once per day thereafter, for a total of 14 days.  Dermal responses were evaluated 24 hours after topical application and on Days 3, 7, 10, and 14 according to the Draize method of scoring.  Application of MRD-83-349 at a dose level of 3160 mg/kg showed no evidence of systemic toxicity under the conditions of this study and all animals survived to study termination.  There were no deaths or treatment-related clinical signs.  Topical exposure elicited very slight to well defined erythema in all animals and very slight edema in four animals.  Desquamation was noted in five animals during the study.  By Day 14, all animals were clear of erythema and edema.  Based on the results of this study, the dermal LD50 for MRD-83-349 is greater than 3160 mg/kg. 

Classification as an acute dermal toxicant is not warranted under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP) or under Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.