N-butylphosphorothioic triamide

Endpoint summary

Description of key information

skin irritation (OECD 404): not irritating
eye irritation (OECD 405): corrosive

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Between 12 August 1994 and 12 October 1994

Reliability:

2 (reliable with restrictions)

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.

Qualifier:

according to guideline

Guideline:

EPA OTS 798.4470 (Acute Dermal Irritation)

Deviations:

no

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

(six animals were tested; first observation was done 4 hours after patch removal instead of 60 minutes)

GLP compliance:

yes

Species:

other: Rabbit (New Zealand White)

Strain:

other: Hra:(NZW)SPF strain

Details on test animals or test system and environmental conditions:

Test Animals:
- Source: from HRP, Inc., Kalamazoo, Michigan
- Age at study initiation: Adult albino rabbits
- Weight at study initiation: 2.4 to 2.9 g
- Housing: the animals were individually housed in screen-bottom stainless steel cage
- Fasting period before study: Not stated
- Diet: a measured amount of Laboratory Rabbit Diet HF #5326, PMI Feeds
- Water: The animals were provided access to water ad libitum.
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 23°C
- Humidity (%): 50 ± 20
- Air changes (per hr): Not stated
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: To:
In-life Start Date: 16 August 1994
In-life Termination Date: 19 August 1994

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Remarks:

was moistened with distilled water

Controls:

other: untreated skin of each animal was used for comparison

Amount / concentration applied:

500 mg (0.5 g)

Duration of treatment / exposure:

4 h

Observation period:

approximately 24, 48, and 72 hour

Number of animals:

6

Details on study design:

TEST SITE
- Area of exposure: 6.25 cm²
- Type of wrap if used: The area of application was covered with a 2.5 x 2.5-cm gauze patch secured with paper tape, loosely overwrapped with Saran Wrap®, and secured with Elastoplast® tape to provide a semiocclusive dressing.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The test sites were washed using tap water and disposable paper towels. The test material was removed from the test sites as thoroughly as possible without irritating the skin.
- Time after start of exposure: At the end of the 4-hour exposure period

SCORING SYSTEM: based on the Draize scoring system

Irritation parameter:

erythema score

Basis:

mean

Remarks:

out of all six animals

Time point:

other: mean over 24, 48 and 72 h

Score:

0.06

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

edema score

Basis:

mean

Remarks:

out of all six animals

Time point:

other: mean over 24, 48 and 72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritant / corrosive response data:

The test material produced only a very slight erythema reaction in one animal. No other dermal irritation was observed. The average of the 4-, 24-, 48- and 72-hour index scores is 0.04 (considered to be slightly irritating). All irritation cleared by the 48-hour observation.
Reversibility of any observed effect: Changes fully reversible within 48 hours (2 days).

Other effects:

None

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Application of N-(n-butyl) thiophosphoric triamide (NBPT) to the skin of rabbits under 4-hour semioccluded conditions resulted in only a very slight erythema reaction in one of six animals. No other dermal irritation was observed. The average of the 4-, 24-, 48-, and 72-hour scores is 0.04 (considered to be slightly irritating). All irritation cleared by the 48-hour observation.

Executive summary:

The objective of this study was to assess the relative level of primary dermal skin irritation of a test material on rabbits under semioccluded conditions. The study was conducted according to EPA guidelines: EPA OTS 798.4470 (Acute Dermal Irritation).

The primary dermal irritation potential of N-(n-butyl) thiophosphoric triamide (NBPT) was evaluated in rabbits under 4-hour semioccluded conditions. The test material produced only a very slight erythema reaction in one of six animals. No other dermal irritation was observed The average of the 4-, 24-, 48- and 72-hour index scores is 0.04 (considered to be slightly irritating). All irritation cleared by the 48-hour observation.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

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.

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

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

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

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.

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)

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

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

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

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.

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.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

The skin irritation/corrosion study was performed equivalent to OECD 404 (Glaza, 1994). The test substance was moistened with water and placed on a gauze patch. The gauze patch was applied to the intact skin of six albino rabbits under semi-occlusive conditions for an exposure periods of 4 h. After the treatment, the gauze patch was removed and the treated skin site was washed with tap water and dried with paper towels. The evaluation of irritant effects was performed at 4, 24, 48 and 72 h after patch removal. Mean erythema score was 0.06 and mean edema score was 0 for all animals over 24, 48 and 72 h. Erythema was fully reversible within 48 hours. Under the test conditions, the test substance was not irritating to the skin.

According to OECD 405, the unchanged test substance was applied in the conjunctival sac of one eye of one rabbit (Sanders, 2001). The untreated eye served as the control. 1, 24, 48 and 72 h after test substance instillation, the grades of ocular reaction (conjunctivae, cornea, iris) were recorded. Conjunctival redness (score 2), chemosis (score 2), iritis (score 1) and corneal opacity (score 1.7) were observed as mean scores for the 24, 48, and 72 h observation period. Iritis was fully reversible within 7 days, conjuntival redness and chemosis within 14 days post application. Corneal opacity was still present at the end of the observation period of 21 days. Iridial inflammation was noted in the treated eye one hour after treatment and at the 24, 48, 72-hour and 7-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. Under the test conditions chosen, and taking the irreversibility of the corneal effects into consideration, the test substance was considered as corrosive to the eyes.

Justification for selection of skin irritation / corrosion endpoint:
Only one study available.

Justification for selection of eye irritation endpoint:
Only one study available.

Effects on eye irritation: corrosive

Justification for classification or non-classification

The available data on skin irritation of the test substance do not meet the criteria for classification according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, but the data on eye irritation do meet the criteria. Therefore the substance is classified as Eye irritant (Cat. 1, H318) according to Regulation (EC) 1272/2008 and Xi (R41) according to Directive 67/548/EEC.