7-[(5-chloro-2,6-difluoro-4-pyrimidinyl)amino]-4-hydroxy-3-[(4-methoxy-2-sulphophenyl)azo]naphthalene-2-sulphonic acid, sodium salt

Respiratory sensitisation

Administrative data

Endpoint:

respiratory sensitisation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

17 Sep - 12 Oct 1990

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1991

Report date:

1991

Materials and methods

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

7-[(5-chloro-2,6-difluoro-4-pyrimidinyl)amino]-4-hydroxy-3-[(4-methoxy-2-sulphophenyl)azo]naphthalene-2-sulphonic acid, sodium salt

EC Number:

286-839-5

EC Name:

7-[(5-chloro-2,6-difluoro-4-pyrimidinyl)amino]-4-hydroxy-3-[(4-methoxy-2-sulphophenyl)azo]naphthalene-2-sulphonic acid, sodium salt

Cas Number:

85391-83-9

Molecular formula:

C21H14ClF2N5O8S2.xNa

IUPAC Name:

7-[(5-chloro-2,6-difluoro-4-pyrimidinyl)amino]-4-hydroxy-3-[(4-methoxy-2-sulphophenyl)azo]naphthalene-2-sulphonic acid, sodium salt

Test material form:

solid: particulate/powder

Details on test material:

Reactive Red 123

Test animals

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Winkelmann, Borchen
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: deduced from weight: 1 - 2 month
- Weight at study initiation: 264 +/-10g
- Housing: Makrolon cage type IV, four animals per cage, caged changed at least once per week
- Diet (e.g. ad libitum): Altromon 3022, ad libitum
- Water (e.g. ad libitum): mains water, ad libitum
- Acclimation period: at least one week after delivery

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

Test system

Route of induction exposure:

intradermal

Route of challenge exposure:

inhalation

Vehicle:

water

Remarks:

for intradermal injection

Concentration:

induction: 3 repetitions of each two-times 100µl of a solution with 5% test substances in water
challenge: nominal 60mg test substance/m³ for 30 minutes

No. of animals per dose:

8 animals per dose and vehicle control

Details on study design:

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3
- Exposure period: intradermal induction on day 0, 2 and 4
- Test groups: one test group
- Control group: one vehicle control
- Site: day 0: cranial; day 2: thoracal; day 4: caudal
- Concentrations: treatment at each exposure: test group: two-times 100µl of a solution with 5% test substance in water; vehicle control: two-times 100µl water

B. CHALLENGE EXPOSURE
- No. of exposures: 2:
- Day(s) of challenge: test group on day 22 and 24; control group on day 21 and 23
- Exposure period: inhalative exposure for ca. 30 minutes, nose/head only
- Test groups: induction exposure with test substance
- Control group: induction exposure with vehicle
- Concentrations: ca. 60mg test substance/m³ (aerosol)
- Evaluation (hrs. after challenge): 20h after challenge, section at test day 25


GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: inhalation chamber
- Exposure chamber volume: ca. 20L
- Method of holding animals in test chamber: fixed in an exposure tube
- Source and rate of air: ca. 80% of added air is exhausted via an aersol filter to have a continues air flow.
- System of generating aerosols: a 0.7% (g/v) test substance water solution is fogged in a pre-chamber (nominal 500mL/m³, results in 3500mg test substance/m³), transfered to inhalation chamber by air flow
- Method of particle size determination: Aerodynamic Particle Sizer with Laser-Velocimeter
- Temperature, humidity, pressure in air chamber: temperature: ca. 22°C, humidity: > 90%
- Brief description of analytical method used: two times 25L air with a flow of 4L/min taken and analysed with gravimetric methods
- Samples taken from breathing zone: yes
- MMAD (Mass median aerodynamic diameter): 0.92µm
- Mass fraction < 3µm: 100%
- particles per cm³: 150315

OTHER:
- assessed endpoints: body weight, clinical signs, pulmunary function testing (breathing rate, breathing volume) for immediate and delayed reactions, section

Results and discussion

Results:

clinical signs: local skin reaction at 6 out of 8 animals during induction exposure in test substance group, no reactions in vehicle group; no reactions during challenge exposure
body weight: not affected
pulmonary function testing (breathing rate, breathing volume) for immediate and delayed reactions: 5 out of 8 animals showed immediate reactions in the test substance group, delayed reactions at 3 out of 8 animals in both groups
section: no lung irritation observed during section, lung weight not affected

Any other information on results incl. tables

treatment	anaphylactic shock	immediate reaction	delayed reaction
vehicle control	0/8	0/8	3/8
test substance	0/8	5/8	3/8
results of challenge exposure animals with reactions/ tested animals

Applicant's summary and conclusion

Interpretation of results:

Category 1 (respiratory sensitising) based on GHS criteria

Conclusions:

The test item showed a potential for respiratory sensitisation in guinea pigs. The substance is classified as Category 1 according to CLP criteria.