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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:
14/12/1982-25/2/1983
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline-compliant, proprietary study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1983

Materials and methods

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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Type:
Constituent
Details on test material:
Yellow powder (sodium chromate)
Orange/red powder (sodium dichromate)
Orange/red powder (potassium dichromate)

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Cheshire Farms, Ltd
- Age at study initiation: 10-12 weeks
- Weight at study initiation: 1.67-2.71 kg
- Fasting period before study: Not stated
- Housing: Individual
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 14 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 10-24
- Humidity (%): 40-82
- Air changes (per hr): Not reported
- Photoperiod (hrs dark / hrs light): Not reported


IN-LIFE DATES: From: 14/12/82 To: 25/2/83

Administration / exposure

Type of coverage:
occlusive
Vehicle:
physiological saline
Details on dermal exposure:
TEST SITE
- Area of exposure: Approximately 26.4 cm2
- % coverage: 10
- Type of wrap if used: occlusive tape


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): 2 g/kg
- Concentration (if solution): moistened with saline (0.15 ml/g)
- Constant volume or concentration used: yes

VEHICLE
- Amount(s) applied (volume or weight with unit): 2 ml/kg
- Concentration (if solution): -
- Lot/batch no. (if required): -
- Purity: -
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
Five
Control animals:
yes, concurrent vehicle
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Daily observation; bodyweights recorded on Days 1, 4, 7, 11 and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, organ weights (brain, lungs, liver, spleen, kidneys, gonads), necropsy
Statistics:
Homogenity of variance (F Max); Student's t-test; Wilcoxon Rank Sum test.

Results and discussion

Preliminary study:
Not reported
Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Remarks on result:
other: Sodium dichromate
Sex:
female
Dose descriptor:
LD50
Effect level:
< 2 000 mg/kg bw
Remarks on result:
other: Sodium dichromate
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Remarks on result:
other: Sodium dichromate
Sex:
male
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Remarks on result:
other: Sodium chromate
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Remarks on result:
other: Sodium chromate
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Remarks on result:
other: Sodium chromate
Sex:
male
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Remarks on result:
other: Potassium dichromate
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Remarks on result:
other: Potassium dichromate
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Remarks on result:
other: Potassium dichromate
Mortality:
Sodium chromate: no males died; one female died on Day 4
Sodium dichromate: One male died on Day 1; three females died on Days 1-6
Potassium dichromate: No males died; two females died between Days 3-6
Clinical signs:
Sodium chromate: Green staining, hypokinesia, sneezing, swellilng of the application site
Sodium dichromate: Yellow staining, hypokineisa, swollen or encrusted application site
Potassium dichromate: Green/blue/yellow.red staining, hunched posture, ataxia, hypothermira, encrusted application site
Body weight:
Bodyweights were variable: no significant differences in bodyweight attributable to treatment were apparent in any of the treated groups.
Gross pathology:
Gross necropsy did not reveal any effects clearly related to treatment in any group.
Other findings:
Mean absolute and relative liver weights were seen in females administered sodium dichromate. No effects were seen on other organ weights and similar effects were not seen in any of the other treated groups.

Any other information on results incl. tables

The significantly lower liver weights seen in females treated with sodium dichromate are not considered to be of toxicological significance as they are associated with low concurrent control values.

Liver weight

Sodium chromate

Controls

Sodium dichromate

Controls

Potassium dichromate

Controls

M

F

M

F

M

F

M

F

M

F

M

F

Absolute (g)

103

111

110

110

111

116**

116

91

106

103

116

98

Relative (%)

4.4

4.9

4.3

4.3

4.3

5.4**

4.1

3.5

4.3

4.8

4.3

4.4

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Acute dermal LD50 values for all of the Cr (VI) compounds investigated in this study were found to be >2000 mg/kg bw (combined sexes). Females appeared to be slightly more sensitive than males to each of the compounds and 3/5 females administered sodium dichromate died.
Executive summary:

Sodium chromate, sodium dichromate and potassium dichromate (moistened with saline) were administered for 24 hours under occluive conditions to the shorn dorsal skin of groups of New Zealand White Rabbits (5/sex). Animals were observed for 14 days.

Deaths occurred in the groups treated with sodium chromate (1F), sodium dichromate (1M, 3F) and potassium dichromate (2F). Signs of systemic toxcity and local dermal effects were observed in each treatment group. Bodywieghts were unaffected by treatment. Gross necropsy did not reveal any clearly treatment-related effects. Significantly higher absolute and relative liver weights seen in sodium dichromate-treated animals are associated with low concurrnet controls and are considered to be of minimal toxicological significance.

The acute dermal LD50 values for each of the compounds investigated was therefore found to be >2000 mg/kg bw.