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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:
02 May 2018 to 25 June 2018
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
OECD Guideline for Testing of Chemicals No. 402 (Section 4: Health Effects) “Acute Dermal Toxicity: Fixed Dose Procedure” adopted on 09 October 2017

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2018
Report Date:
2018

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
OECD Guideline for Testing of Chemicals No. 402 (Section 4: Health Effects) “Acute Dermal Toxicity: Fixed Dose Procedure” adopted on 09 October 2017
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
fixed dose procedure
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid: viscous
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- batch No.of test material: 18-UH-0703
- Expiration date of the batch: March 2020


STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Ambient (21 to 29°C)

FORM AS APPLIED IN THE TEST (if different from that of starting material): As such based on individual animal body weight

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: In-house
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 10 weeks
- Weight at study initiation: 201.16 g to 214.88 g
- Fasting period before study: no
- Housing: standard polypropylene cage (size: L 430 x B 285 x H 150 mm)
- Diet (e.g. ad libitum): Altromin maintenance diet for rats and mice (manufactured by Altromin Spezialfutter GmbH & Co. KG)
- Water (e.g. ad libitum): Deep bore-well water passed through Reverse osmosis unit
- Acclimation period: 04 May 2018 to 13 May 2018

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.6°C to 22.9°C
- Humidity (%): 47% to 65%
- Air changes (per hr): 12 to 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours fluorescent light and 12 hours dark cycle

IN-LIFE DATES: From: 04 May 2018 To: 28 May 2018

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
water
Details on dermal exposure:
TEST SITE
- Area of exposure: dorso-lateral area of the trunk of the animals
- % coverage: approximately 10% of the total body surface
- Type of wrap if used: non-irritating adhesive tape

REMOVAL OF TEST SUBSTANCE
- Washing (if done): washed using distilled water and dried with absorbent cotton
- Time after start of exposure: 24 hours

Duration of exposure:
The contact period of test item was about 24 hours
Doses:
2000 mg/kg body weight
No. of animals per sex per dose:
Range finding study : 1 Female
Main study : 2 Females
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: All the animals were observed for clinical signs of toxicity and mortality at 20 to 30 min, 1 hr (±10 mins), 2 hrs (±10 mins), 4 hrs (±10 mins) and 6 hrs (±10 mins) post dosing on Day 1 and thereafter once daily for clinical signs of toxicity and twice daily for mortality during the 14 days observation period.
Individual animal body weight was recorded at receipt, on day 1 before test item application and on day 8 and 15 during the experimental period.
- Necropsy of survivors performed: yes

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
no indication of skin irritation up to the relevant limit dose level
Mortality:
No mortality
Clinical signs:
No clinical signs
Body weight:
No treatment related changes in body weight and percent change in body weight with respect to day 1 were noted. Normal increase in body weights were noted during the observation period
Gross pathology:
No treatment related gross pathological changes were noted at 2000 mg/kg body weight (range finding study and main study) during necropsy

Any other information on results incl. tables

TABLE 1.     CLINICAL SIGNS OF TOXICITY ANDMORTALITY RECORD

Phase of the Experiment

 

Dose (mg/kg body weight)

Animal No.

Sex

Time of Dosing

(AM)

Clinical Signs of Toxicity and Mortality on Day 1

Clinical Signs of Toxicity and Mortality on days

20-30

mins

1 hr

(±10 mins)

2 hrs

(±10 mins)

4 hrs

(±10 mins)

6 hrs

(±10 mins)

2

3

4

5

6

7

8

9

10

11

12

13

14

15

Range Finding Study

2000

Rc9161

F

10:50

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Main Study

2000

Rc9162

F

10:39

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

Rc9163

F

10:41

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

N

    N: Normal; F: Female; min: minutes; hr/hrs: hour/hours


TABLE 2.   BODY WEIGHT (g) AND PERCENT CHANGE IN BODY WEIGHT WITH RESPECT TO DAY 1

Phase of the Experiment

Dose (mg/kg)

Animal No.

Sex

Body Weight (g) on Days

Percent Change in Body Weight with Respect to Day

1

8

15

1 to 8

1 to 15

Range Finding Study

2000

Rc9161

F

219.53

235.60

251.73

 

7.32

14.67

Main Study

2000

Rc9162

F

241.43

256.34

270.98

 

6.18

12.24

Rc9163

F

230.94

246.70

262.14

6.82

13.51

Mean

236.19

251.52

266.56

 

6.50

12.87

±SD

7.42

6.82

6.25

 

0.46

0.90

 

 

n

 

2

2

2

 

2

2

     F: Female; SD: Standard Deviation; n: Number of animals

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 


TABLE 3.    GROSS PATHOLOGY FINDINGS

Phase of the Experiment

Dose

(mg/kg body weight)

Animal No.

Sex

Fate

Gross Pathology Findings

External

Internal

Range finding Study

2000

Rc9161

F

TS

NAD

NAD

Main Study

2000

Rc9162

F

TS

NAD

NAD

Rc9163

F

TS

NAD

NAD

 NAD: No Abnormality Detected; F: Female;TS: Terminal Sacrifice

Applicant's summary and conclusion

Interpretation of results:
Category 5 based on GHS criteria
Conclusions:
Under the experimental conditions employed and based on the above results, it is concluded that the acute dermal median lethal dose (LD50) of test item 6-(Isononanoylamino) hexanoic acid, compound with 2,2′,2″-nitrilotriethanol (1:1) in Sprague Dawley rats is > 2000 mg/kg body weight and classified as “Category 5 / Unclassified” (2000 < ATE ≤ 5000 mg/kg body weight) according to the Globally Harmonized System (GHS) of Classification
Executive summary:

The test item 6-(Isononanoylamino) hexanoic acid, compound with 2,2′,2″-nitrilotriethanol (1:1) obtained from Clariant India Ltd.was evaluated for Acute Dermal Toxicity in Sprague Dawley Rats as per the OECD guideline for the testing of chemicals No. 402, “Acute Dermal Toxicity - Fixed Dose Procedure”.

The study was performed in two phases i.e. range finding study and main study. Range finding study was performed with one female rat and main study was performed with two female rats. On the day before the application of the test item, fur on the dorso-lateral area of the trunk of the animals was removed by clipping closely with an electric hair clipper and care was taken to avoid abrading the skin.

The required quantity of the test item was applied as uniform film over an area of approximately 10% of the total body surface. The test item was held on to the applied surface by covering with cotton gauze dressing and wrapped with non-irritating adhesive tape and finally the application site was wrapped using semi-occlusive crepe bandage. The contact period of test item was 24 hours. At the end of the contact period, the residual test item was washed using distilled water and dried with absorbent cotton.

Since the oral LD50of test item is >2000 mg/kg for rats as per material safety data sheet provided by the sponsor, a starting dose of 2000 mg/kg body weight was selected from the fixed dose levels of 50, 200, 1000 and 2000 mg/kg body weight. No clinical signs and mortalities were observed at the dose level of 2000 mg/kg body weight in range finding study. Hence, during main study, two animals were administered with the same dose level of 2000 mg/kg body weight. No clinical signs were observed at the dose level of 2000 mg/kg body weight. Hence, no further testing was carried out.

All the animals were observed for clinical signs of toxicity and mortality at 20 to 30 min, 1 hr (±10 mins), 2 hrs (±10 mins), 4 hrs (±10 mins) and 6 hrs (±10 mins) on treatment day 1 and thereafter once daily for clinical signs of toxicity and twice daily for mortality during the 14 days observation period. The body weight was recorded on day 1 before test item application and on day 8 and 15. At the end of observation period, all the animals were sacrificed under carbon dioxide anaesthesia and subjected to necropsy and detailed gross pathological examination.

No mortality, clinical signs and skin reactions were noted. No treatment related changes in body weight and percent change in body weight with respect to day 1 were noted. Normal increase in body weights were noted during the observation period. No treatment related gross pathological changes were noted at 2000 mg/kg body weight (range finding study and main study) during necropsy.