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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Endpoint:
respiratory sensitisation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1990-10-15 to 1991-01-18
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1991
Report date:
1991

Materials and methods

Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
The method is based according to Karol et al. 1985, Karol et al. 1978, DeCeaurriz et al. 1987, Barrow et al. 1977, Botham et al. 1988, Botham et al. 1989.
The exposure criteria are according to OECD 403. The corresponding EC directive is fulfilled as far as it relevant for this type of study. General recommendations on the measurement technique (ASTM E 981-84, ALARIE, 1973) were taken into account.
GLP compliance:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
4-(benzoylamino)-6-[[5-[[(5-chloro-2,6-difluoro-4-pyrimidinyl)amino]methyl]-1-sulpho-2-naphthyl]azo]-5-hydroxynaphthalene-1,7-disulphonic acid, lithium sodium salt
EC Number:
280-426-3
EC Name:
4-(benzoylamino)-6-[[5-[[(5-chloro-2,6-difluoro-4-pyrimidinyl)amino]methyl]-1-sulpho-2-naphthyl]azo]-5-hydroxynaphthalene-1,7-disulphonic acid, lithium sodium salt
Cas Number:
83400-11-7
Molecular formula:
C32 H21 Cl F2 N6 O11 S3 . x Li . x Na C32H(21-x-y)ClF2Li(x)N6Na(y)O11S3
IUPAC Name:
4-(benzoylamino)-6-[[5-[[(5-chloro-2,6-difluoro-4-pyrimidinyl)amino]methyl]-1-sulpho-2-naphthyl]azo]-5-hydroxynaphthalene-1,7-disulphonic acid, lithium sodium salt
Test material form:
solid: particulate/powder

Test animals

Species:
guinea pig
Strain:
Pirbright-Hartley
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Versuchstierzucht Winkelmann, Borchen, Germany
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 1-2 months
- Weight at study initiation: 245 ± 16 g
- Housing: Makrolon-cages type IV (4 animals per cage); cages were cleaned once a week and disinfected with Zephirol (10%), Litter: wooden granular (Typ S 8/15; Ssniff - Spezialdiaten GmbH, D 4770 Soest)
- Diet (e.g. ad libitum): ad libitum; fixed formula standard diet Altromin 3022
- Water (e.g. ad libitum): ad libitum; tap water
- Acclimation period: at least one week
- Indication of any skin lesions: only health and symptom free animals were used for the study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): ca. 50
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12 / 12

Test system

Route of induction exposure:
intradermal
Route of challenge exposure:
inhalation
Vehicle:
water
Remarks:
levatit water
Concentration:
intradermal induction: 5% test item in water
No. of animals per dose:
8
Details on study design:
MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3 times intradermal application, 2 applications, each of 100 µL (Monday (day 0): cranial, Wednesday: thoracal, Friday: caudal)
- Test groups: 100 µL of 5% test item in water, two applications
- Control group: 100 µL water, two applications
- Site: on the flank, Day 0: cranial, Day 2: thoracal, Day 4: caudal
- Concentrations: 5% solution of the test item in water.

B. CHALLENGE EXPOSURE
- No. of exposures: single exposure for 30 min with the aerosol
As only 4 animals could be exposed simultaneously control group (1a) was exposed on day 21, control group (2a) was exposed on day 22, test item group (1b) was exposed on day 23 and test item group (2b) was exposed on day 24.
The exposure concentrations were: 1a: 26 mg/m³, 2a: 28 mg/m³, 1b: 24 mg/m³ and 2b: 29 mg/m³
- Evaluation: Lung function: peak expiratory flow (PEF), respiratory rate volume (TV), respiratory rate per minute (RR), respiratory minute volume (MV), inspiration time (IT), expiration time (ET)

OTHER:
Body weights:
Body weights were taken befor the 1st application, on day 3 and 7 afterwards once per week

Clinical Signs:
Animals were observed at least once per day

Necropsy:
On day 25 the animals were sacrificed and analysed by gross pathology. The weight of the lung were taken.
Challenge controls:
yes
Positive control substance(s):
none
Negative control substance(s):
none

Results and discussion

Results:
Induction:
No test item-related effects; but local skin reactions at the injection site (encrusted and hardened skin)

Challenge:
no clinical effects

Lung function tests:
In 3 of 8 exposed animals effects of pulmonary hypersensitivity were observed. This was characterized by a modified respiratory minute volume and a disproportionate increase in the expiratory time. Delayed pulmonary reactions were observed in 4 of 8 animals.

Body weight:
There were no changes in body weights observed.

Gross pathology:
No effects were observed in any animals.

Lung weights:
No changes in lung weights were observed in any animals.
Positive control results:
n.a.
Negative control results:
No effects were observed in vehicle control animals.

Any other information on results incl. tables

Table 2: Number of Animals with positive reaction during challenge phase

Induction Anaphylaxie Immediate Delayed
Vehicle 0/8 0/8 0/8
Test item 0/8 3/8 4/8

Applicant's summary and conclusion

Interpretation of results:
Category 1 (respiratory sensitising) based on GHS criteria
Conclusions:
In this study, the test item showed a sensitising potential in lungs of guinea pigs.
Executive summary:

In a respiratory sensitization study with the test item, young adult female Pirbright-White-Dunkin-Hartley guinea pigs (8/group) were tested for respiratory sensitisation. The animals were treated intradermally with the test item 5% in water. After three weeks the control and test item group animals were challenged with a 30 min inhalation exposure with the test item. In 3 of 8 exposed animals effects of pulmonary hypersensitivity were observed. Delayed pulmonary reactions were observed in 4 of 8 animals. No effects in body and lung weights were observed compared to the control. No gross pathological findings were observed. According to this study, the test item is a respiratory sensitizer.