Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
10 May 2018 - 06 November 2018
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Guideline study performed under GLP. All relevant validity criteria were met.

Data source

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

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
24 February 1987
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
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:
solid
Details on test material:
Storage Conditions:Stable at ambient temperature (10-30°C). Store in darkness; may be used/formulated in light.

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Envigo RMS (UK) Limited, Oxon, UK
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 8 - 12 weeks
- Weight at study initiation: body weight variation did not exceed ±20% of the mean body weight at the start of treatment
- Fasting period before study: not specified
- Housing: individually housed in suspended solid floor polypropylene cages furnished with softwood flake bedding.
- Diet (e.g. ad libitum): free access to food (2014C Teklad Global Rodent diet supplied by Envigo RMS (UK) Limited, Oxon, UK)
- Water (e.g. ad libitum): free access to mains drinking water
- Acclimation period: minimum of 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25 ºC
- Humidity (%): 30 - 70 %
- Air changes (per hr): minimum of 15 changes per hour
- Photoperiod (hrs dark / hrs light): 12 : 12

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: back and flanks of each animal were clipped free of hair.
- % coverage: Approximately 10% of total body surface
- Type of wrap if used: A piece of surgical gauze was placed over the treatment area and semi‑occluded with a piece of self‑adhesive bandage.

REMOVAL OF TEST SUBSTANCE
- The treated skin and surrounding hair wiped with cotton wool moistened with arachis oil BP and distillled water to remove any residual test item.
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount applied: 2000 mg/kg bw
- Constant volume or concentration used: Undiluted
Duration of exposure:
24h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations and mortality checks were conducted at approximately 0.5, 1, 2, 4, hours and subsequently once daily for 14 days. Full details on the scoring and criteria (consistent with Draize) are given in the full study report. Individual bodyweight were recorded prior to application of the test item on Day -1 (before dosing) and on Days 0, 1 and 14.
- Necropsy of survivors performed: yes
Statistics:
n/a

Results and discussion

Effect levels
Key result
Sex:
male/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:
There were no deaths.
Clinical signs:
There were no signs of systemic toxicity.
Body weight:
All animals showed expected gains in body weight.
Gross pathology:
No abnormalities were noted at necropsy.

Any other information on results incl. tables

Table 1.  Clinical Observations and Mortality Data

 

Dose

(mg/kg bw

 

 

Mortality

(# dead / total)

 

Time range of deaths

(hours)

 

 

Number with evident toxicity

(# / total)

 

Male

Female

Combined

Male

Female

Combined

 2000

0/5

0/5

0/10

n/a

0/5

0/5

0/5

Table 2.  Dermal effects Noted After Initiation of Exposure

 

Days after exposure

 

 Erythema(#/ total)

 Edema(# / total)

Other(# / total)

Male

Female

Male

Female

Male

Female

1

0/5

0/5

0/5

0/5

5/5 (BrBl)

5/5 (Bl)

2

0/5

0/5

0/5

0/5

5/5 (Br)

0/5

3

0/5

0/5

0/5

0/5

5/5 (Br)

0/5

4

0/5

0/5

0/5

0/5

5/5 (Br)

0/5

5

0/5

0/5

0/5

0/5

5/5 (Br)

0/5

6-14

0/5

0/5

0/5

0/5

0/5

0/5

0 =       No reactions

 Bl=       Blanching of the skin

 Br=       Light brown discoloration of the epidermis

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of this study the dermal LD50 was established to exceed 2000 mg/kg bw in male & female Wistar (RccHan:WIST) strain rat. Applicant assessment indicates, under the conditions of this study, and according to the GHS criteria, the LD50 cut-off value was considered to be greater than 5000 mg/kg body weight.
Executive summary:

A study was performed according to OECD TG 402; Acute Toxicity (Dermal) and in accordance with GLP to assess the acute dermal toxicity of the test substance in the Wistar (RccHan:WIST)  strain rat.  A group of ten animals (five males and five females) were given a single, 24 hour, semi‑occluded dermal application of the test item to intact skin at a dose level of 2000 mg/kg body weight  for a duration of 24 hour under semi-occluded condition and sequent observation for 14 days.

There was no mortality during the study. There were no signs of system toxicity or abnormalities on necropsy. All animals showed expected gains in body weight during the study. Very slight erythema, blanching of the skin and light brown discoloration of the epidermis were noted during the observation period. Treated skin sites of female animals appeared normal two days after treatment and of male animals six days after treatment.

Under the conditions of this study the dermal LD50 was established to exceed 2000 mg/kg bw in Wistar (RccHan:WIST) strain rat. Applicant assessment indicates, under the conditions of this study, and according to the GHS criteria, the LD50 cut-off value was considered to be greater than 5000 mg/kg body weight.