N-butylphosphorothioic triamide

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Between 30 July 2001 and 20 August 2001.

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2001

Report date:

2001

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Date of GLP inspection: 28 February 2000, Date of Signature on GLP certificate: 26 April 2000

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

435-740-7

EC Name:

-

Cas Number:

94317-64-3

Molecular formula:

C4H14N3PS

IUPAC Name:

Phosphorothioic triamide, N-butyl-

Constituent 2

Reference substance name:

N-(n-butyl) thiophosphoric triamide (NBPT)

IUPAC Name:

N-(n-butyl) thiophosphoric triamide (NBPT)

Details on test material:

Sponsor's identification: NBPT
Description: white powder
Batch number: C2001-01
Date received: 19 July 2001
Storage conditions: at approximately 4°C in the dark

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: David Percival Ltd, Moston, Sandbach, Cheshire, UK
- Age at study initiation: Twelve to sixteen weeks old
- Weight at study initiation: 2.0 to 3.5 kg
- Housing: The animals were individually housed in suspended cages. The animals were provided with environmental enrichment items which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.
- Diet: STANRAB SQC Rabbit Diet, Special Diets Services Ltd, Witham, Essex, UK
- Water: Free access to mains drinking water
- Acclimation period: At least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 23°C
- Humidity (%): 30 - 70%
- Air changes (per hr): At least fifteen changes per hour
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: The left eye remained untreated and was used for control purposes.

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): A volume of 0.1 mL of the test material, which was found to weigh approximately 80 mg (as measured by gently compacting the required volume into an adapted syringe) was placed into the conjunctival sac of the right eye, formed by gently pulling the lower lid away from the eyeball.
- Concentration (if solution): Not applicable. Test material was used as supplied.

VEHICLE
- Amount(s) applied (volume or weight with unit): Not applicable
- Concentration (if solution): Not applicable
- Lot/batch no. (if required): Not applicable

Duration of treatment / exposure:

single application without washing

Observation period (in vivo):

Approximately 1 hour and 24, 48 and 72 hours following treatment. Additional observations were made on Days 7, 14 and 21 to assess the reversibility of the ocular effects.

Number of animals or in vitro replicates:

1

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Not applicable
- Time after start of exposure: Not applicable

SCORING SYSTEM: Assessment of ocular damage/irritation was made approximately 1 hour and 24, 48 and 72 hours following treatment, according to the numerical evaluation from Draize.

TOOL USED TO ASSESS SCORE: Examination of the eye was facilitated by the use of the light source from a standard ophthalmoscope.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal #1

Remarks:

120Male

Time point:

other: Mean 24, 48 and 72 hours

Score:

1.7

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: Area of cornea involved: 4 (1, 24, 48, 72 hous and 7 days post application); 1 (day 14 and 21 post application)

Results 2

Irritation parameter:

iris score

Basis:

animal #1

Remarks:

120 Male

Time point:

other: Mean 24, 48 and 72 hours

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 7 days

Results 3

Irritation parameter:

conjunctivae score

Basis:

animal #1

Remarks:

120 Male

Time point:

other: Mean 24, 48 and 72 hours

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 14 days

Results 4

Irritation parameter:

chemosis score

Basis:

animal #1

Remarks:

120 Male

Time point:

other: Mean 24, 48 and 72

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 14 days

Results 5

Irritation parameter:

other: Discharge

Basis:

animal #1

Remarks:

120 Male

Time point:

other: Mean 24, 48 and 72

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 14 days

Irritant / corrosive response data:

Dulling of the normal lustre of the cornea was noted in the treated eye one hour after treatment. Scattered or diffuse corneal opacity was noted at the treated eye at the 24-hour observation with translucent corneal opacity at the 48, 72-hour and the 7 and 14-day observations. Scattered or diffuse corneal opacity was noted in the treated eye at the 21-day observation.

Iridial inflammation was noted in the treated eye one hour after treatment and at the 24, 48, 72-hour and 7-day observations.

Moderate conjunctival irritation was noted in the treated eye one hour after treatment and at the 24, 48, 72-hour, 7 and 14-day observations.

Vascularisation, with a generalised ingrowth of vessels for approximately 3 to 4 mm, was noted in the treated eye at the 7, 14 and 21-day observations with ectropion also noted in the treated eye at the 14-day observation.

Cornea effects noted at the 21-day observation were considered to be irreversible.

Other effects:

Body weight: All animals showed expected gain in bodyweight during the study.

Applicant's summary and conclusion

Interpretation of results:

corrosive

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

CLP: Eye irrit 1, H318
DSD: Xi, R41

Executive summary:

Introduction. The study was performed to assess the irritancy potential of the test material to the eye of the New Zealand White rabbit. The method was designed to meet the requirements of the following:

-OECD Guidelines for the Testing of Chemicals No. 405 "Acute Eye Irritation/Corrosion" (adopted 24 February 1987)

-Commission Directive 92/69/EEC Method B5 Acute Toxicity (Eye Irritation)

Result. A single application of the test material to the non-irrigated eye of one rabbit produced irreversible effects. Reactions noted included translucent corneal opacity, iridial inflammation, moderate conjunctival irritation, dulling of the normal lustre of the cornea, ectropion and vascularisation with a generalised ingrowth of vessels for approximately 3 to 4 mm. Corneal opacity was not reversible within the observation period of 21 days.

Conclusion. The test material produced irreversible effects and was considered to be corrosive to the rabbit eye.

The test material was also considered to be irritant according to EU labelling regulations Commission Directive 93/21/EEC. It is reasonable to assume that the symbol "Xi", the indication of danger "Irritant" and the highest risk phrase R 41 "RISK OF SERIOUS DAMAGE TO EYES" are therefore required. Under the GHS it is classified under the health hazard category "Eye Damge 1" with a hazard statement H318: Causes serious eye damage.