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Description of key information

One key study for acute oral toxicity with sodium dichromate is available.

No study is available for acute inhalation toxicity with sodium dichromate. However, based on the information available from acute inhalation toxicity with another chromium (VI) category substance (potassium dichromate), it was concluded using a category read-across concept that the formal data requirements are fulfilled. The approach for read-across is described in detail in the document attached in IUCLID section 13.

One key study for acute dermal toxicity with sodium dichromate is available.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
17/1/1983-23/2/1983
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
no
Remarks:
Pre-dates GLP
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River, UK
- Age at study initiation: 7-9 weeks
- Fasting period before study: 18h
- Housing: Individual
- Diet: ad libitum except pre-dosing period
- Water: ad libitum
- Acclimation period: 14 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-21
- Humidity (%): 24*-74
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 5% w/v
- Amount of vehicle (if gavage): variable
- Justification for choice of vehicle: solubility of test material
Doses:
Sodium dichromate: 0.2, 0.5, 1.5, 3.0 and 5.0 ml/kg; equivalent to 10, 25, 75, 150 and 250 mg/kg bw
No. of animals per sex per dose:
Five/sex
Control animals:
yes
Details on study design:
Animals were administered a single gavage dose and observed for 14 days. Rats were weighed on Days 1, 4, 7, 11 and 14. Gross necropsy was performed on all animals, weights of the brain, lungs, liver, spleen, kidneys and gonads were recorded. Tissue samples were taken at necropsy, however no histopathology was performed.
Statistics:
Homogeneity of variance was establised using the F-max test, follwoed by Student;s t-test or Wilcoxon Rank Sum test.
Preliminary study:
Dose levels of 0.2, 1.0, 2.0, 4.0 and 6.0 ml/kg bw were used; equivalent to 10, 50, 100, 200 and 300 mg/kg bw. Deaths occurred at >=200 mg/kg bw
Sex:
male
Dose descriptor:
LD50
Effect level:
123.5 mg/kg bw
95% CL:
> 107 - < 142.5
Remarks on result:
other: Sodium dichromate
Sex:
female
Dose descriptor:
LD50
Effect level:
86.5 mg/kg bw
95% CL:
> 74 - < 101
Remarks on result:
other: Sodium dichromate
Mortality:
In the main study, mortality occurred at dose levels of >=75 mg/kg bw (females) and >=150 mg/kg bw (males) within two days of dosing
Clinical signs:
Piloerection, hypothermia, hunched posture, hyperkinesia, hypokinesia, prostration, ataxia, diarrhoea, sedation, coma, tremors, epistaxis, soiled coat (30 minutes-6 days)
Body weight:
Weight gain was initially reduced in the surviving male rats at 25, 75 and 150 mg/kg bw.
Gross pathology:
Reddened gastric mucosa with abnormal (green) coloring and contents; green areas on lungs
Other findings:
Organ weights were unaffected by treatment with any compound

Dose level

Mortality

ml/kg bw

mg/kg bw

males

females

6.0

0

0

0

0.2

10

0

0

0.5

25

0

0

1.5

75

0

1

3.0

150

5

4

5.0

300

4

5

Interpretation of results:
Category 3 based on GHS criteria
Conclusions:
According to the classification criteria of CLP regulation (EC) 1272/2008 and subsequent regulations sodium dichromate is classified as acute oral toxic Category 3 with the signal word "Danger" and the hazard statement "H301-Toxic if swallowed".
Executive summary:

Groups of rats (5/sex) were gavaged with single doses of sodium dichromate (in water) at dose levels of between 10 and 300 mg/kg bw. Animals were observed for 14 days. Body weights were recorded on Days 1, 4, 7, 11 and 14. Gross necropsy was performed on all animals and organ weights recorded.

Deaths occurred at dose levels of >=75 mg/kg bw: females were slightly more sensitive than males. Signs of toxicity were observed in all groups and included hunched posture, tremors, hypokinesia, sedation, prostration, coma, piloerection, ataxia, diarrhoea, dacryorrhoea and hyperkinesia. Slightly reduced weight gain was seen in some surviving animals. Findings at necropsy were limited to reddening and staining of the stomach, abnormal gastric contents and green staining of the lungs. Organ weights were unaffected by treatment.

LD 50 values were calculated to be 123.5 (107.0 -142.5) mg/kg bw in males; 86.5 (74.0 -101.0) mg/kg bw in females.

According to the classification criteria of CLP regulation (EC) 1272/2008 and subsequent regulations sodium dichromate is classified as acute oral toxic Category 3 with the signal word "Danger" and the hazard statement "H301-Toxic if swallowed".

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
86.5 mg/kg bw
Quality of whole database:
Key study available.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
adverse effect observed

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
14/12/1982-25/2/1983
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
no
Remarks:
Pre-dates GLP
Test type:
standard acute method
Limit test:
yes
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals or test system 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
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.
Preliminary study:
Not reported
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.

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

Interpretation of results:
Category 4 based on GHS criteria
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
Acute dermal LD50 values for sodium chromate and potassium dichromate were investigated in this study were found to be >2000 mg/kg bw (combined sexes). In case of sodium dichromate females appeared to be slightly more sensitive than males. The acute dermal LD50 values for sodium dichromate were >2000 mg/kg bw/day and <2000 mg/kg bw/day for males and females, respectively. Since the lowest LD50 in this study is <2000 mg/kg bw/day, sodium dichromate needs to be classified as acutely toxic via the dermal route, category 4, H312: Harmful in contact with skin (Signal word: Warning). This classification is in line with the legal classification of sodium dichromate (index number 024-004-00-7).
Executive summary:

Sodium chromate, sodium dichromate and potassium dichromate (moistened with saline) were administered for 24 hours under occlusive 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 toxicity and local dermal effects were observed in each treatment group. Body weights 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 concurrent controls and are considered to be of minimal toxicological significance.

Acute dermal LD50 values for sodium chromate and potassium dichromate were investigated in this study were found to be >2000 mg/kg bw (combined sexes). In case of sodium dichromate females appeared to be slightly more sensitive than males. The acute dermal LD50 values for sodium dichromate were >2000 mg/kg bw/day and <2000 mg/kg bw/day for males and females, respectively.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
Key study available.

Additional information

One key study with sodium dichromate is available for acute oral and dermal toxicity. No study with sodium dichromate is available for acute inhalation toxicity. The discussion of all endpoints is included in the endpoint summary of the hexavalent chromium substances and the read-across approach is described in detail in the attached document in section 13 of the IUCLID.

Justification for classification or non-classification