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Toxicological information

Repeated dose toxicity: dermal

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Administrative data

Endpoint:
short-term repeated dose toxicity: dermal
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report Date:
2012

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 410 (Repeated Dose Dermal Toxicity: 21/28-Day Study)
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Test compound : “Pigment Voilet-27”
Characteristics : Blue powder
Purity : 93% min.

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:


Environmental conditions: The animals were kept in air conditioned rooms with 10-15 air circulation cycle per hour, temperature between 22-250C, relative humidity 40-60% and illumination cycle set to 12 hours artificial fluorescent light and 12 hours dark.

Accommodation: Groups of five animals of similar sex in polypropylene cages with stainless steel grill top, facilities for food and water bottle and bedding of clean paddy husk.

Diet: Pelleted feed supplied by Pranav agro Industries Ltd., B7/6 Ramesh Nagar, Delhi, India

Water: Community tap water passed through ‘Aqua Guard on line water filter’, was kept in glass bottles, ad-libitum

Administration / exposure

Type of coverage:
occlusive
Vehicle:
water
Details on exposure:
The three dose levels of test compound (62.5, 250 & 1000 mg/kg b.wt) were used to confirm the sub acute dermal toxicity. The 1000 mg/kg b.wt is the highest dose for sub acute toxicity study
Duration of treatment / exposure:
28 days
Frequency of treatment:
The test substance was applied uniformly daily over an area approximately 10 per cent of the total body surface area in graduated doses for a period of 28 days. Between applications the test substance is held in contact with the skin with a porous gauze dressing and non-irritating tape. The test site was covered in a suitable manner to retain the gauze dressing and test substance and ensure that the animals cannot ingest the test substance.
No. of animals per sex per dose:
5 male and 5 female in test and control group
Control animals:
yes
Details on study design:
Age of test organisms: 8 to 10 weeks
Body weight range: 200±20g
Identification : By cage tag and corresponding colour body marking
Dose groups : Four + one control
Group - I Vehicle control
Group - II 62.5 mg/kg b. wt
Group - III 250 mg/kg b. wt
Group - IV 1000 mg/kg b.wt
Group - V 1000 mg/kg b.wt (Reversal group)
Acclimatization: The selected healthy wistar albino rats were acclimatized to standard laboratory condition under the supervision of Veterinarian for period of one week.
Randomization: After acclimatization and Veterinary examination the animals randomly divided into four groups viz, one control and three treatment group.
Nutritional conditions: Animals were fasted overnight prior to test compound administration and food was offered three hours after dosing.

Examinations

Observations and examinations performed and frequency:
The toxicity of the test compound following dermal application was assessed. Five male & five female rats were used per step for each dose level. The rats were observed for incidence of mortality and signs of intoxication for 28 days after the administration of test article.
Sacrifice and pathology:
GROSS PATHOLOGY: Yes, During necropsy all the organs viz; Adrenals, Brain, Heart, Kidneys, Liver, Lungs, intestine, Spleen, lymph nodes and Testes of body were examined for gross pathological changes.

HISTOPATHOLOGY: Yes, Samples of following organs and tissues were processed for histopathological examination Adrenals, Brain, Heart, Kidneys, Liver, Lungs, intestine, Spleen and Testes.
Other examinations:
Observations were made for moratality, clnical signs, body weight, food intake, haematobiochemical study, urine analysis, terminal studies, absolute organ weight,
Statistics:
The data obtained from present investigation were analyzed by One Way ANOVA and Tukey HSD Test.

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Description (incidence and severity):
The wistar albino rats treated with the Pigment Violet-27 at the different dose levels of 62.5, 250 and 1000 mg/kg b.wt did not show any mortality throughout the period of observation (28 days)
Mortality:
no mortality observed
Description (incidence):
The wistar albino rats treated with the Pigment Violet-27 at the different dose levels of 62.5, 250 and 1000 mg/kg b.wt did not show any mortality throughout the period of observation (28 days)
Body weight and weight changes:
no effects observed
Description (incidence and severity):
The body weight of wistar albino rats treated with different dose levels (62.5, 250 & 1000 mg/kg b.wt) of Pigment Violet-27 recorded on day 0, 7th, 14th, 21st and 28th did showed normal change in body weight as compared to the control group.
Food consumption and compound intake (if feeding study):
no effects observed
Description (incidence and severity):
The food intake gm/cage calculated weekly on day 7th, 14th, 21st and 28th did not show significant changes upto highest tested dose level 1000 mg/kg b.wt of test compound Pigment Violet-27as compared to the control group.
Haematological findings:
no effects observed
Description (incidence and severity):
The test compound Pigment Violet-27did not show significant change in red blood cell count upto highest tested dose level 1000 mg/kg b.wt as compared to the control group
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
no effects observed
Organ weight findings including organ / body weight ratios:
no effects observed
Description (incidence and severity):
The organ weight of each rat observed on day 28th - Adrenals, Brain, Ovaries, Heart, Testes, Spleen, Kidney, Liver and Lungs did not reveal any significant (p>0.05) change at different tested dose levels (62.5, 250 & 1000 mg/kg b.wt) compared to control
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
no effects observed

Effect levels

Dose descriptor:
NOEL
Effect level:
1 000 mg/kg bw/day
Based on:
test mat.
Sex:
male/female

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
The result obtained from present study can be concluded the test compound Pigment Violet-27 is sub acutely non toxic to wistar albino rat upto the dose level 1000 mg/kg b.wt applied dermally for a period of 28 days.
Executive summary:

The result obtained from present study can be concluded the test compound Pigment Violet-2 7is sub acutely non toxic to wistar albino rat upto the dose level 1000 mg/kg b.wt applied dermally for a period of 28 days.