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Administrative data

Description of key information

NOAEL > 1000  mg/kg bw/day at 30 days

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records
Reference
Endpoint:
short-term repeated dose toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From january 15 to february 28, 1979
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: No GLP, aged study.
Qualifier:
no guideline followed
Deviations:
not applicable
Principles of method if other than guideline:
1000 mg/kg/day of the substance where administrated daily (5 times a week) by gavage over a period of 30 days to male and female rats.
GLP compliance:
no
Limit test:
yes
Species:
rat
Strain:
other: Tif: RAIf (SPF)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: 4 weeks
- Weight at study initiation: 128-129 g, female; 113-115 g males
- Housing: the animals were housed individually in Macrolon cages type 3 with standardized granulated soft wood bedding (Socicté Parisicnne des sciures Pantin).
- Diet: Pelleted standard diet (Nafag. No. /890) ad Libitum

Neither insecticides nor chemicals were applied in the animal room with the exceptic of a desinfectant: Fungitex SB (Prod. Nr. 30071, Ciba-Geigy).

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 1°C
- Humidity (%): 55 ± 5%
- Air changes (per hr): 15-17
- Photoperiod (hrs dark / hrs light): 10/10
Route of administration:
oral: gavage
Details on oral exposure:
PREPARATION OF DOSING SOLUTIONS:
Volume: 10 ml/kg of a daily prepared suspension (10 % compound in Carboxymethyl-cellulose 2 %)
The animals of group 1 (Control) received a similar treatment with CMC 2 % without the compound.
Duration of treatment / exposure:
4 weeks and 2 days of the 5th week (30 days)
Frequency of treatment:
5 times at week (in total 22 doses); 1 dose per day for 4 weeks plus in the 5th week on Monday to Tuesday
Remarks:
Doses / Concentrations:
0/1000
Basis:
no data
No. of animals per sex per dose:
20 males, 20 females per experimental group
Control animals:
yes, concurrent vehicle
Observations and examinations performed and frequency:
MORTALITY: Yes, daily

SYMPTOMS: Yes, daily

BODY WEIGHT: Yes, weekly

FOOD CONSUMPTION: Yes, weekly

EYE EXAMINATION: Yes, by observation prior to dosing and after the treatment period

HEARING TEST: prior to dosing and after the treatment period (by hand clapping)

MEAN FOOD CONSERVATION: was calculated according the following formula: MFC = (weekly food consumption in g / midweek body weight) x (1000/7)

Haematologic, blood chemistry and urinalysis measurements were carried out by standard methods on 20 randomized rats (5 males, 5 females per group) from the control and one test group at test day 28.
To reduce the biologic variability due to circadian rhythms, blood sampling for haematology and blood chemistry was between the hours of 8.00 and 9.00 a.m. For blood chemistry measurements food was withheld overnight prior to blood removal. The site of blood removal was the orbital sinus and a micro-
haematocrit glass capillary tube was used.
Blood samples from each animal with the respective anticoagulant (EDTA for performing haematologleal and heparin for blood chemistr measurements) were aliquoted into individual vials.
No anaesthesia was used to restrain the animals. All blood collection was by manual restraint only.
Urine for analysis was collected overnight. The individual rats were housed in special metabolism cages.
Food and water was withheld during the time of urine collection.
The quantitative assay of all blood parameters was completed within a 8 h. period under "Quality Control" conditions.
Statistics:
For each time point and parameter a uni-variate statistical analysis was conducted. Due to the routine manner of the analysis system parameter free methods were applied. The treated group was compared to the control group in respect of dispersion and displacement.
Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Description (incidence and severity):
Comparable to the controls
Food efficiency:
no effects observed
Description (incidence and severity):
Comparable to the controls
Haematological findings:
no effects observed
Description (incidence and severity):
Unremarkable
Clinical biochemistry findings:
no effects observed
Description (incidence and severity):
Unremarkable and comparable to those of the controls
Urinalysis findings:
no effects observed
Description (incidence and severity):
Unremarkable
Organ weight findings including organ / body weight ratios:
no effects observed
Description (incidence and severity):
No statistically significant
Details on results:
During the experiment no treatment realted reactions were observed with respect to clinical symptoms, mortality, food consumption, body weight, clinacl laboratory investigations and pathology.
Eye examination did not reveal any ocular changes. No loss hearing ability was registred.

At the end of the 30 day toxicity study or after an additional recovery period of two weeks the treated rats showed neither macroscopical nor microscepical changes which could be related to the treatment with FAT 11 11o/N.
Dose descriptor:
NOEL
Effect level:
> 1 000 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Critical effects observed:
not specified

Macroscopical Findings:

All details regarding the gross anatomical changes are listed within the macroscopical findings in individual rats. No compound related gross anatomical changes were noted.

Microscopical Findings:

All details regarding the histopathological changes are listed within the microscopical findings in individual rats. All minor changes seen in some control and treated rats and described within the microscopical findings in individual rats were only incidental in nature and not related to the treatment with FAT 11 110/N.

Conclusions:
It can be concluded from the observations made during the study that 1000 mg/kg/day of FAT 11'110/N produced no observable effects in male and female rats when administrated daily by gavage over a period of 30 days.
Executive summary:

The toxicity of FAT 11'110/N was investigated during a period over 30 day on females and males rats by oral administration.

No observable effects were observed at a dosage of 1000 mg/kg/day.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
1 000 mg/kg bw/day
Study duration:
subchronic
Species:
rat

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Leist (Leist, 1982) and Dystar (Dystar, 1979) studies, respectively at 28 and 30 days, don't report a limit dose for Direct Red 23 (DR23), but identify No-Observed-Adverse-Effect-Level (NOAEL) as > 1000 mg/kg. In the other Dystar study it has been concluded that the no toxic effect level (NOEL) of DR23, when fed to rats for 6 months, was 750 ppm in the diet, or 37.5 mg/kg body weight/day; nevertheless in the same study has been stressed that the effects found at the 1500 and 3000 ppm levels were only weak, aspecific and of doubtful, if any biological significance.

Leist (Leist ,1982) and Dystar (Dystar, 1979) studies are more reliable than the Dystar supporting study, thus the key value chose was the NOAEL > 1000 mg/kg.


Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
Subacute study (30 days) on Direct Red 23 of which results have been confirmed in the Leist et al. 1982 study.

Justification for selection of repeated dose toxicity inhalation - systemic effects endpoint:
Based on REACH regulation annex VIII column 2 (specific rules for adaptation from column 1) the study does not need to be conducted if exposure of humans via inhalation is unlikely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size.

Justification for selection of repeated dose toxicity inhalation - local effects endpoint:
Based on REACH regulation annex VIII column 2 (specific rules for adaptation from column 1) the study does not need to be conducted if exposure of humans via inhalation is unlikely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size.

Justification for selection of repeated dose toxicity dermal - systemic effects endpoint:
Based on REACH regulation annex VIII column 2 (specific rules for adaptation from column 1) the study does not need to be conducted if exposure of humans by dermal route is unlikely; physicochemical and toxicological properties don't suggest potential for a significant rate of absorption through the skin

Justification for selection of repeated dose toxicity dermal - local effects endpoint:
Based on REACH regulation annex VIII column 2 (specific rules for adaptation from column 1) the study does not need to be conducted if exposure of humans by dermal route is unlikely; physicochemical and toxicological properties don't suggest potential for a significant rate of absorption through the skin

Justification for classification or non-classification

According to CLP regulation (EC1272/2008) Direct Red 23 is not classified for subacute toxicity.