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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:
2016-11-03 to 2017-02-17
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2016
Report Date:
2017

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: Males 8 weeks old; Females 9 weeks old
- Weight at study initiation: Males 267.5-283.4g; Females 217.6-231.5g
- Housing: one animal per cage
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: for four days after three days of quarantine (including health examinations)

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.1-24.6°C (measured), permissible range 19.0-25.0°C
- Humidity (%): 47.7-61-7% (measured), permissible range 30.0-70.0%
- Air changes (per hr): 10-15 clean, fresh, filtered air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours light/12 hours dark

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: dorsal surface
- % coverage:
- Type of wrap if used: lint, Soft Cloth Tape with Liner and surgical tape

REMOVAL OF TEST SUBSTANCE
- Washing (if done): cotton moistened with tepid water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2.25 mL/kg bw
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5 animals per sex per dose;
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations for mortality, clinical signs, general conditions at 30 minutes after dosing and at 1, 2, 4, 6 hours after dosing on day 0 and once daily thereafter for 14 days; body weight was recorded prior to dosing on day 0 and on day 1, 3, 7, and on day of necropsy, day 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: no histopathology, since no gross findings were observed at necropsy.
Statistics:
Statistical analysis was performed using SAS progam V9.3.

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
All animals at 2000 mg/kg bw and in the control group survived the duration of the study. There were no effects on the mortality. (see table 1)
Clinical signs:
All animals at 2000 mg/kg bw and in the control group showed no abnormalities of clinical signs. (see table 2)
Body weight:
A decrease in body weight was observed in one female on day 3 and in another female on day 14 in the control group and in three females on day 3 in the 2000 mg/kg bw group. This effect was not considered to be a test sustance related- effect because there were no clinical signs or necropsy findings indicating morphologic abnormalities. (see table 3)
Gross pathology:
No grossly visible evidence of morphological abnormalities were observed in any animal at 2000 mg/kg bw or in the control group.

Any other information on results incl. tables

Table 1: Summary of Mortality

Sex

dose (mg/kg)

No. animals

Days after dosing

mortality

 

 

 

0

1

2

3

4

5

6

7

8

9

10

11

12

13

14

 

male

0

5

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0/5

 

2000

5

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0/5

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Female

0

5

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0/5

 

2000

5

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0/5

Table 2: Individual Clinical Signs

Sex

Dose (mg/kg)

No. animals

Clinical sign

Hours (day 0) after dosing

 

 

 

 

0.5

1

2

4

6

Male

0

5

NOA

5

5

5

5

5

 

2000

5

NOA

5

5

5

5

5

 

 

 

 

 

 

 

 

 

Female

0

5

NOA

5

5

5

5

5

 

2000

5

NOA

5

5

5

5

5

Sex

Dose (mg/kg)

No. animals

Clinical sign

Days after

 

 

 

 

1

2

3

4

5

6

7

8

9

10

11

12

13

14

Male

0

5

NOA

5

5

5

5

5

5

5

5

5

5

5

5

5

5

 

2000

5

NOA

5

5

5

5

5

5

5

5

5

5

5

5

5

5

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Female

0

5

NOA

5

5

5

5

5

5

5

5

5

5

5

5

5

5

 

2000

5

NOA

5

5

5

5

5

5

5

5

5

5

5

5

5

5

NOA: No observable abnormality

Table 3: Individual Body Weights

Sex

Dose

 

Days after dosing

Gain

 

 

 

0

3

7

14

0-14

Male

0

Mean

274.9

288.3

315.7

358.1

83.2

 

 

S.D.

3.2

1.9

6.9

12.8

12.4

 

 

N

5

5

5

5

5

 

2000

Mean

276.0

284.1

305.2

344.9

68.9

 

 

S.D.

6.8

10.2

12.1

18.9

14.1

 

 

N

5

5

5

5

5

 

 

 

 

 

 

 

 

Female

0

Mean

225.5

228.0

237.2

248.4

22.9

 

 

S.D.

4.9

3.2

7.5

14.0

10.0

 

 

N

5

5

5

5

5

 

2000

Mean

226.3

227.6

239.2

254.4

28.2

 

 

S.D.

7.0

2.4

4.4

5.2

8.7

 

 

N

5

5

5

5

5

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Based on the result of the acute dermal study in Sprague-dawley rats, the test substance has an LD50 value greater than 2000 mg/kg bw.
Executive summary:

The purpose of this study was to assess the potential toxicity and the approximate LD50 value of the test substance following a single dermal application to Sprague-Dawley rats.

 

Test groups consisted of one dose group at a dose of 2,000 mg/kg and a control group, and each group consisted of 5 males and 5 females. All animals were monitored for clinical signs and body weight changes after dosing during the 14-day observation period. They were subjected to gross necropsy at the end of the observation period.

 

There were no deaths of animals in the 2,000 mg/kg groups. No test substance-related effects were observed in clinical signs, body weight data or necropsy findings in the 2,000 mg/kg groups.

 

Based on the result of this study, the LD50 value of the test substance was considered to be greater than 2,000 mg/kg in male and female rats under the conditions of this study. Therefore, it was not classified according to CLP.