Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
other information
Study period:
1961
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
The study is not reliable because of several methodological deficiencies: number of the animal tested per sex is too low (2 animals per sex); the test is performed on animals of both sexes; weight of the animals dosed is lower in comparison to that recommended in OECD TG 402; the doses used are not spaced accurately; observation period is too short, microscopic analysis was not performed; individual weights of the animals were determined just at the end of the observation period; the size of the skin area treated is not reported; the test material is applied to the closely clipped intact abdominal skin under a dental damming binder placed around the trunk of the animal. Due to these deficiencies this data source is not considered acceptable for assessment. However, according to OECD SIDS, a reliability 2 was given.

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1992
Report Date:
1992
Reference Type:
secondary source
Title:
Unnamed
Year:
2004

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
2 male and 2 female albino rabbits were exposed to 100, 316, 1000, 3160 mg/kg bw of dimethyl phosphonate for 24 hours. Animals were observed for mortality and toxic effects. Autopsy was performed. Animals at lowest and highest dosage were observed for signs of dermal irritation.
GLP compliance:
no
Remarks:
GLP was not mandatory at the time of the study
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): dimethyl phosphonate
- Physical state: liquid (colourless, liquid)
- Analytical purity: not reported

Test animals

Species:
rabbit
Strain:
other: albino
Sex:
male/female

Administration / exposure

Type of coverage:
other: dental damming binder placed around the trunk
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: trunk
- Type of wrap if used: dental damming binder placed around the trunk.


REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes
Duration of exposure:
24 hours
Doses:
100, 316, 1000, 3160 mg/kg.
No. of animals per sex per dose:
2 (only 2 males and 2 females are used per dose group)
Control animals:
no
Details on study design:
- Duration of observation period following administration: immediately, 1 h, 24 h, once daily for a total of 7 days.
- Examinations performed: mortality, toxic effects, autopsy, animals at lowest and highest dosage were observed for signs of dermal irritation.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
681 mg/kg bw
Based on:
test mat.
Mortality:
Deaths occurred in dose groups 1000 (4/4) and 3160 (3/4) mg/kg bw 2 and 3 days after application.
Clinical signs:
48 h after application >= 1000 mg/kg bw: depression, ptosis, labored respiration, ataxia, placidity.
Body weight:
No data
Gross pathology:
NECROPSY FINDINGS: hemorrhagic lungs, red-tinged fluid in the pleural cavity, congestion of the thymus and kidneys, oedema or thickening of the mucosa of the stomach, inflammation of a portion of the intestines (1000 and 3160 mg/kg bw). Dermal effects: no signs of irritation.

Applicant's summary and conclusion

Interpretation of results:
other: study not relavant for assessment
Conclusions:
The dermal LD50 in male and female rabbits was 681 mg/kg, which is lower than the oral LD50 in rats and mice, and which may point to the fact that the rabbit may be a more sensitive species.
Executive summary:

Occidental Chemical Corporation (1992)

In an acute dermal study male and female rabbits (2 males and 2 females) were expose to 100, 316, 1000, 3160 mg/kg of dimethyl phosphonate for 24 hours. Animals were observed for mortality and toxic effects. Autopsy was performed. Animals at lowest and highest dosage were observed for signs of dermal irritation. The dermal LD50 in male and female rabbits was 681 mg/kg bw. Signs of intoxication were depression, ptosis, labored respiration, ataxia and placidity at doses of >= 1000 mg/kg bw. At necropsy (concentrations of> or = 1000 mg/kg bw) hemorrhagic lungs, red-tinged fluid in the pleural cavity, congestion of the thymus and kidneys, edema or thickening of the mucosa of the stomach, and inflammation of a portion of the intestines were observed.

The dermal LD50 in male and female rabbits was 681 mg/kg, which is lower than the oral LD50 in rats and mice, and which may point to the fact that the rabbit may be a more sensitive species.

The study is not reliable because of several methodological deficiencies: number of the animal tested per sex is too low (2 animals per sex); the test is performed on animals of both sexes; weight of the animals dosed is lower in comparison to that recommended in OECD TG 402; the doses used are not spaced accurately; observation period is too short, microscopic analysis was not performed; individual weights of the animals were determined just at the end of the observation period; the size of the skin area treated is not reported; the test material is applied to the closely clipped intact abdominal skin under a dental damming binder placed around the trunk of the animal. Due to these deficiencies this data source is not considered acceptable for assessment