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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:
October 3, 2013 - October 17, 2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study has been performed according to OECD and/or EC guidelines and according to GLP principles.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2013
Report Date:
2013

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
(1987)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
(2008)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Version / remarks:
(1998)
Deviations:
no
Qualifier:
according to
Guideline:
other: Food and Agricultural Materials Inspection Centre (FAMIC), 12 Nohsan, Notification No. 8147, April 2011; including the most recent partial revisions.
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): 5-(Sodiosulfo)isophthalic Acid
- Description: White powder
- Expiration date of the batch: 24 February 2015
- Storage condition of test material: At room temperature in the dark
- pH: 2.3 (1% in water)
- Water solubility: 0.345 g/mL

Test animals

Species:
rat
Strain:
other: Wistar strain, Crl:WI (Han)
Sex:
male/female
Details on test animals and environmental conditions:
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: Young adult animals (approx. 10 weeks old)
- Weight at study initiation: Body weight variation was within +/- 20% of the sex mean (males: 297-342 g; females: 204-233 g)
- Housing: Individually in labeled Macrolon cages
- Diet: Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany).
- Water: Free access to tap water.
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 – 24
- Humidity (%): 40 - 70
- Air changes (per hr): approx 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: October 3, 2013 - October 17, 2013

Administration / exposure

Type of coverage:
occlusive
Vehicle:
water
Details on dermal exposure:
- Clipping: One day before exposure (Day -1) an area of approximately 5x7 cm on the back of the animal was clipped
- Application: The formulation was applied in an area of approx. 10% of the total body surface, i.e. approx. 25 cm² for males and 18 cm² for females. The formulation was held in contact with the skin with a dressing, consisting of a surgical gauze patch, successively covered with aluminum foil and Coban elastic bandage. A piece of Micropore tape was additionally used for fixation of the bandages in females only.
- Frequency: Single dosage, on Day 1
- Washing: Following application, dressings were removed and the skin cleaned of residual test substance using tap water.
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw

No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
VEHICLE
- Justification for choice of vehicle: The vehicle was selected based on trial formulations performed at WIL Research Europe and on test substance data supplied by the sponsor.

Dose volume: 2000 mg/kg (10 mL/kg) body weight.

DOSAGE PREPARATION: The formulation (w/w) was prepared within 4 hours prior to dosing. Homogeneity was accomplished to a visually acceptable level.

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality/Viability: Twice daily
Body weights: Days 1 (pre-administration), 8 and 15
Clinical signs: At periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15
(only the results of the clinical observation on Day 5 were not recorded, but the study integrity was not affected, since sufficient data was available)
- Necropsy of survivors performed: Yes

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No mortality occurred
Mortality:
No mortality occurred
Clinical signs:
- Chromodacryorrhoea (snout) was noted in the majority of animals between Days 1 and/or 2 (grade 1)
- Yellow discoloration of the treated skin site was noted in all animals during the observation period
Body weight:
- Incidences of slight body weight loss or reduced body weight gain were seen in females during the first week post treatment. All females regained weight during the second week, except for one female that showed some body weight loss during the second week
- The changes noted in body weight gain in males were within the range expected and were therefore considered not indicative of toxicity
Gross pathology:
Macroscopic examination of the animals did not reveal any abnormalities.
Other findings:
None reported

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In an acute dermal toxicity study with rats, performed according to OECD/EC test guidelines, the LD50 >2000 mg/kg bw was determined for the substance.
Executive summary:

The acute dermal toxicity of the substance was determined in the rat, in accordance with OECD 402 (1987) and according to GLP principles. The substance was administered to five Wistar rats of each sex by a single dermal application of 2000 mg/kg bw for 24 hours. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice. No mortality occurred. Chromodacryorrhoea (snout) was noted in the majority of animals between Days 1 and/or 2 (grade 1), as well as yellow discoloration of the treated skin site in all animals during the observation period. Incidences of slight body weight loss or reduced body weight gain were seen in females during the first week post treatment. Macroscopic examination of the animals did not reveal any abnormalities. The dermal LD50 value of the substance in Wistar rats was established to be >2000 mg/kg bw. Based on the results, the substance does not have to be classified for acute dermal toxicity according to the CLP Regulation.