Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
23 September - 07 October 2003
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP-Guideline Study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2003
Report Date:
2003

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 (incl. certificate)
Test type:
other: single dose

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
other: liquid
Details on test material:
- Name of test material (as cited in study report) : Nicotinsäurepentylester HF
- Substance type : organic
- Physical state : pale yellow liquid
- Analytical purity : 95%
- Purity test date : 2003-07-24
- Lot/batch No. : 03030417/005
- Storage condition of test material : room temperature

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS : Sprague Dawley rats (SPF Caw)
- Source : Elevage JANVIER (53940 Le Genest-St-Isle – France)
- Age at study initiation : not stated
- Weight at study initiation : 208 - 237 g (males) ; 163 - 204 g (females)
- Housing : not stated
- Diet (e.g. ad libitum): rat and mouse maintenance diet
- Water (e.g. ad libitum) : not stated
- Acclimation period : 5 days

ENVIRONMENTAL CONDITIONS
- Temperature : 19-23°C
- Humidity : 44-65%
- Air changes (per hr) : not stated
- Photoperiod (hrs dark / hrs light) : not stated

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure : no information available
- % coverage : no information available
- Type of wrap if used : porous gauze

REMOVAL OF TEST SUBSTANCE
- Washing (if done) : The treated area was rinsed at 24 hours with distilled water

TEST MATERIAL
- Amount(s) applied (volume or weight with unit) : 9,61 ml/kg
- Constant volume or concentration used : yes
Duration of exposure:
24 hours
Doses:
10000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
other: yes , control animals received an effective dose of 10000 mg/kg bw of distilled water
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: clinical observations were recorded 1, 3, 5, 24 and 48 hours after dosing and regularly subsequently for fourteen days, Individual bodyweights were recorded prior to application of the test material on day 0, day 2 and on days 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

All animals were subjected to gross necropsy.

Results and discussion

Preliminary study:
No mortality occurred during the preliminary study.
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 10 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred during the study .
Clinical signs:
Neither systemic nor cutaneous clinical signs related to the administration of the test item were observed.
Body weight:
The body weight evolution of the animals remained normal throughout the study, similar between treated and control animals.
Gross pathology:
The macroscopical examination of the animals at the end of the study did not reveal treatment-related changes.
Other findings:
No other findings were reported.

Any other information on results incl. tables

Observation data sheet No. 1 - Group 2 (treated)

Treatment : 10000 mg/kg body weight

OBSERVATIONS
T0 + 1 hour
T0 + 3 hours
T0 + 5 hours
MALES FEMALES
Rm
3999
Rm
4000
Rm
4001
Rm
4002
Rm
4003
Rf
4004
Rf
4005
Rf
4006
Rf
4007
Rf
4008
Spontaneous activity N N N N N N N N N N
Preyer’s reflex (noise) N N N N N N N N N N
Respiratory rate N N N N N N N N N N
Convulsions N N N N N N N N N N
Tremors N N N N N N N N N N
Body temperature N N N N N N N N N N
Muscle tone N N N N N N N N N N
Palpebral opening N N N N N N N N N N
Pupil appearance N N N N N N N N N N
Salivation N N N N N N N N N N
Lachrymation N N N N N N N N N N
Righting reflex N N N N N N N N N N
Back hair appearance N N N N N N N N N N
MORTALITY 0 0 0 0 0 0 0 0 0 0
Remarks None None

Observation data sheet No. 2 - Group 2 (treated)

Treatment : 10000 mg/kg body weight

OBSERVATIONS
T0 + 24 hour
T0 + 48 hours
MALES FEMALES
Rm
3999
Rm
4000
Rm
4001
Rm
4002
Rm
4003
Rf
4004
Rf
4005
Rf
4006
Rf
4007
Rf
4008
Spontaneous activity N N N N N N N N N N
Preyer’s reflex (noise) N N N N N N N N N N
Respiratory rate N N N N N N N N N N
Convulsions N N N N N N N N N N
Tremors N N N N N N N N N N
Body temperature N N N N N N N N N N
Muscle tone N N N N N N N N N N
Palpebral opening N N N N N N N N N N
Pupil appearance N N N N N N N N N N
Salivation N N N N N N N N N N
Lachrymation N N N N N N N N N N
Righting reflex N N N N N N N N N N
Back hair appearance N N N N N N N N N N
Treatment site N N N N N N N N N N
MORTALITY 0 0 0 0 0 0 0 0 0 0
Remarks The treated area was rinsed at 24 hours with distilled water The treated area was rinsed at 24 hours with distilled water

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The study was performed according to the OECD TG402 without deviations and therefore considered to be of the highest quality (reliability Klimisch 1).The test material did not induce any signs of acute dermal toxicity. The test material was considered to be not toxic via the dermal exposure route under the conditions of the test.
Executive summary:

The item Nicotinsäurepentylester HF was applied onto the intact skin of 10 Sprague Dawley rats (5 males and 5 females) at the single dose of 10000 mg/kg body weight according to the experimental protocol established on the basis of the official method as defined in the O.E.C.D. guideline. N° 402 dated February 24th, 1987 and the test method B.3 of the directive. N° 92/69/EEC dated December 29th, 1992.

No mortality occurred during the study. Neither systemic nor cutaneous clinical signs related to the administration of the test item were observed. The body weight evolution of the animals remained normal throughout the study, similar between treated and control animals. The macroscopical examination of the animals at the end of the study did not reveal treatment-related changes.

In conclusion, the LD50 of the item Nicotinsäurepentylester HF is higher than 10000 mg/kg body weight by dermal route in the rat.

According to the criteria for classification, packaging and labelling of dangerous substances and preparations in accordance with the E.E.C. Directives 67/548, 2001/59 and 99/45, the item Nicotinsäurepentylester HF must not be classified.