Alkanes, C14-20

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

1992/11/10-1992/11/24

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable well-documented study report which meets basic scientific principles: GLP

Justification for type of information:

The justification for read across is provided as an attachment in IUCLID Section 13.

Cross-reference

Cross-reference 1

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:

1992/11/10-1992/11/24

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable well-documented study report which meets basic scientific principles: GLP

Justification for type of information:

The justification for read across is provided as an attachment in IUCLID Section 13.

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

reference to other study

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Mortality:

There were no animal deaths prior to study termination.

Clinical signs:

other: Well-defined erythema was noted upon removal of the test patches in all animals exposed to MRD-92-405, with edema noted in two animals. At Day 14, three animals were noted as having very slight erythema and only one animal was noted as having well-defined

Gross pathology:

One animal was free of macroscopic abnormalities. Five animals were observed with desquamation.

Interpretation of results:

other: Not classified

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

The LD50 of MRD-92-405 was > 5000 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, C11-C14, n-alkanes, <2% aromatics based on analogue read across.

Three male and three female rabbits were exposed to MRD-92-405 for 24h via an occluded patch.  Dermal evaluations occurred at 24 hours post patch removal and once daily until the study termination at day 14. Exposure had no affect on viability; all animals survived the exposure.  The LD50 of MRD-92-405 was > 5000 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.

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1993

Report date:

1993

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

; 1987 Guidelines

Deviations:

yes

Remarks:

occlusive dressing used

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Hydrocarbons, C11-C14, n-alkanes, < 2% aromatics

IUPAC Name:

Hydrocarbons, C11-C14, n-alkanes, < 2% aromatics

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 Research Products
-Sex: Male (3); Female (3)
- Age at study initiation: 12-13 weeks
- Weight at study initiation: Male: 2.01 to 2.21 kg; Female: 2.17 to 2.48 kg
- Housing: individually housed
- Diet (e.g. ad libitum): AgwayCertified Diet RCA Rabbit, ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 8-day acclimatization

ENVIRONMENTAL CONDITIONS
- Temperature (°F): 65-70
- Humidity (%): 40 to 60
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

On the day prior to application the trunk of each animal was clipped free of hair. For each treated animal, 5000 mg/kg of MRD-92-405 was applied to the trunk beneath a gauze patch and secured by an occlusive wrap to prevent evaporation. The whole patch assembly was held in place with tape. The patches were left in position for approximately 24 hours. Residual test material was removed and animals were observed 1, 2.5, and 4 hours after dosing and once per day thereafter for a total of 14 days.

Duration of exposure:

24 hours

Doses:

5000 mg/kg: (3) males; (3) female

No. of animals per sex per dose:

Animals: (3) males; (3) female

Control animals:

no

Details on study design:

SCORING SYSTEM: Draize scale
- Dermal response observations: daily
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

Differences between treated and control group mean values for bodyweight gain were analysed by Student's t-test. Where individual variance ratios were significant (P <0.05 or less), Cochrans approximation was applied (Snedecor and Cochran, Statistical Methods, 6th Ed. Iowa State. 1973). Where zero variance was found in one or more groups, intergroup comparison was performed by the Wilcoxon Rank Sum Test.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Mortality:

There were no animal deaths prior to study termination.

Clinical signs:

other: Well-defined erythema was noted upon removal of the test patches in all animals exposed to MRD-92-405, with edema noted in two animals. At Day 14, three animals were noted as having very slight erythema and only one animal was noted as having well-defined

Gross pathology:

One animal was free of macroscopic abnormalities. Five animals were observed with desquamation.

Applicant's summary and conclusion

Interpretation of results:

other: Not classified

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

The LD50 of MRD-92-405 was > 5000 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:

Three male and three female rabbits were exposed to MRD-92-405 for 24h via an occluded patch.  Dermal evaluations occurred at 24 hours post patch removal and once daily until the study termination at day 14. Exposure had no affect on viability; all animals survived the exposure.  The LD50 of MRD-92-405 was > 5000 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.