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Description of key information

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Dose descriptor:
LD50
Value:
1 208 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Dose descriptor:
LC50
Value:
1.08 mg/m³

Acute toxicity: via dermal route

Endpoint conclusion
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Additional information

7.2.1 Acute oral toxicity studies

 

Two acute oral toxicity data studies (see Table 3.2 below) indicate that sodium Pyrithione meets the criteria for classification as harmful by the oral route (LD50 = 965 mg/kg, R22 Harmful if swallowed.). The two most significant studies are discussed below.

 In a GLP study to OECD 401 by Allen DJ (1996) [reference 7.2.1.001, ESPTF 6011-001 ] the results were as follows:

 

Mortality was noted during the day of dosing and up to 2 days after dosing. Signs of systemic toxicity were noted in all dosed groups. Surviving animals recovered 3 to 8 days after dosing.
Surviving animals gained weight during the study.


Necropsy of the decedents revealed haemorrhagic or abnormally red lungs, dark liver or patchy pallor of the liver, dark kidneys and haemorrhage of the gastric mucosa, slight haemorrhage of the small intestine also noted in one female. Necropsy of the animals killed at study termination showed no macroscopically visible findings except for one female treated with 1265 mg.

 

 LD50females: 1208 (965 - 1512) mg active ingredient/kg b.w.

 

According to the EU classification criteria Sodium Pyrithione should be classified as harmful and the symbol Xn and risk phrase R22- harmful if swallowed.

 

In a GLP Study carried out underUS EPA Series 81-1 criteria by Cerven DR (1997):[reference 7.2.1.002 , ESPTF 6011-002 ] the results were:

 

Mortality was noted during the day of dosing and up to 7 days after dosing. Signs of systemic toxicity were noted in all dosed groups. Surviving animals recovered 3 to 8 days after dosing. Surviving animals gained weight during the study except one male dosed at 2000 mg/kg.


Necropsy of the decedents revealed aemorrhagic or abnormally red lungs, dark liver or patchy pallor of the liver, dark kidneys and hemorrhage of the gastric mucosa.
 Necropsy of the animals sacraficed at study termination showed similar findings but to a lesser degree with the majority of surviving animals showing no macroscopically visible findings.

 

 LD50male/females: 1500 (1300 - 1700) mg 40% sodium Omadine/kg b.w.

 

According to the EU classification criteria Sodium Omadine should be classified as harmful and the symbol Xn and risk phrase R22- harmful if swallowed.

 

According to the EU classification criteria Sodium Pyrithione should be classified as harmful and the symbol Xn and risk phrase R22- harmful if swallowed.

 

7.2.2 Acute inhalation toxicity studies

 

One inhalation toxicity study has been carried out (see Table 3.2 below).

 

In a GLP compliant whole body study, Drummond (1987), [reference 7.2.2.001, ESPTF 6013-001], carried out to US EPA Series 81-3 criteria the results were as follows:

Mortality was seen at all of the exposure levels, with most of the deaths occurring on the first day post dose. Toxicologically significant pharmacotoxic signs, such as labored breathing, were noted at all exposure levels. Due to high mortality at the higher dose levels, body weight effects could only be assessed at the two lowest doses. Weight gain was depressed at both doses during the two-week post-exposure period. Pulmonary congestion was the most common macroscopic observation at necropsy. No gross pulmonary abnormalities were seen in animals that survived the observation period. 

It should be noted that these values were likely exacerbated by ingestion of the test substance and so the values determined should be considered very much worst case.

A combined LC50value (males + females) of 1.08 mg/L (95% confidence limits = 0.71 – 1.66 mg/L)

 

The substance is classified as harmful and assigned the risk phrase R20 Harmful by inhalation

7.2.3 Acute dermal toxicity studies

Acute dermal toxicity studies (see Table 7.2.1 below) have been carried out in both rats and rabbits. These studies indicate that the dermal route of exposure warrants no classification.

In a GLP study with rats, conducted to OECD 402 criteria by Bernat E (2001)[reference 7.2.3.001, ESPTF 6012-001], the results were as follows:


No other than local toxic effects of the test substance (eschar formation) were noted during the study. All animals gained weight in both weeks after administration. No abnormalities at necropsy and no mortality were detected.
LD50: > 2000 mg/kg.

 

According to the EU classification criteria Sodium Omadine should not be classified for dermal toxicity.

In a GLP study with rabbits, conducted to US EPA FIFRA series 81-2 criteria by Cerven DR (1987) [reference 7.2.3.002, ESPTF 6012-002], the results were as follows:

 

Clinical signs of emaciation , few feces, ptosis, unkempt appearance, diarrhea, alopecia, ataxia, bloated abdomen, soiling of the anogenital area, pupilary dilation, wetness and yellow staining of the fore limbs, yellow nasal discharge, and alopecia.

The combined male and female dermal LD50is 1800 mg 40% Sodium Omadine/kg b.w.


According to the EU classification criteria Sodium Pyrithione should be classified as harmful and the symbol Xn and risk phrase R21- harmful in contact with skin.

Table 7.2.1        Summary of acute toxicity

Route

Method
Guideline

Species
Strain
Sex
no/group

dose levels
duration of exposure

Value
LD50 or LC50

Remarks

Reference

Oral

Sodium Pyrithion:

40% Aqueous solution of sodium pyrithione

OECD 401: Acute Oral Toxicity
Directive 92/69/EEC, B.1.
Directive 93/21/EEC

GLP (self certification

by the laboratory)

Rat

Sprague-Dawley CD,

5 males and 5 females in the 2000 mg/kg dose group
5 females each in the 800 and 1265 mg/kg groups

800, 1265 and 2000 mg active ingredient/kg b.w

14 days post exposure

period

LD50females: 1208 (965 - 1512) mg active ingredient/kg b.w.

Mortality was noted during the day of dosing and up to 2 days after dosing.
Signs of systemic toxicity were noted in all dosed groups. Surviving animals recovered 3 to 8 days after dosing.
Surviving animals gained weight during the study.
Necropsy of the decedents revealed haemorrhagic or abnormally red lungs, dark liver or patchy pallor of the liver, dark kidneys and haemorrhage of the gastric mucosa, slight haemorrhage of the small intestine also noted in one female. Necropsy of the animals killed at study termination showed no macroscopically visible findings except for one female treated with 1265 mg.

Key Study

 

7.2.1.001

 

ESPTF 6011-001

 

Allen DJ (1996)

(unpublished).

 

Oral,

Sodium Omadine®:

40% aqueous solution of sodium pyrithione

 

US EPA Series 81-1: Acute Oral Toxicity
GLP self certification by laboratory

Rat

Wistar albino

5 males and 5 females per dose

 

1000; 1100; 1200; 1500; 1900; 2000; and 2500 mg 40% Sodium Omadine/kg of bw

Females: 1100 mg/kg b.w

Males: 2000 mg/kg b.w.

Combined Males & Females: 1,500 mg/kg b.w. (1300 – 1700 mg/kg)

Mortality was noted during the day of dosing and up to 7 days after dosing.
Signs of systemic toxicity were noted in all dosed groups. Surviving animals recovered 3 to 8 days after dosing.
Surviving animals gained weight during the study except one male dosed at 2000 mg/kg.
Necropsy of the decedents revealed aemorrhagic or abnormally red lungs, dark liver or patchy pallor of the liver, dark kidneys and hemorrhage of the gastric mucosa.
 Necropsy of the animals sacraficed at study termination showed similar findings but to a lesser degree with the majority of surviving animals showing no macroscopically visible findings.

 

7.2.1.002

 

ESPTF 6011-002

 

Cerven DR (1987)

(unpublished)

Dermal

Natrium Pyrion:

sodium pyrithione solid

>92.5%

OECD 402: Acute dermal Toxicity
Directive 92/69/EEC, B.3.
Directive 93/21/EEC

GLP (self certification

by the laboratory)

Rat

Sprague-Dawley CD

5 per sex

2000 mg a.i./kg bw

(limit test).

14 days post

exposure period

LD50>2000 mg/kg bw

No other than local toxic effects of the test substance (eschar formation) were noted during the study. All animals gained weight in both weeks after administration. No abnormalities at necropsy and no mortality were detected.

7.2.3.001

 

ESPTF 6012-001

 

Bernat E (2001)

(unpublished)

Dermal

Sodium Omadine® 40% aqueous solution

US EPA FIFRA Series 81-2: Acute dermal Toxicity
GLP (self certification

by the laboratory)

New Zealand albino rabbits

5 per sex

1500, 1650, 1800, & 2000 mg/kg

combined male and female dermal LD50is 1800 mg 40% Sodium Omadine/kg b.w.

Clinical signs of emaciation , few feces, ptosis, unkempt appearance, diarrhea, alopecia, ataxia, bloated abdomen, soiling of the anogenital area, pupilary dilation, wetness and yellow staining of the fore limbs, yellow nasal discharge, and alopecia.

Key Study

 

7.2.3.002

 

ESPTF 6012-002

 

Cerven DR (1987)

 

(unpublished)

Inhalation

(whole body)

40% (nominal) solution of sodium Omadine (active ingredient).

Environmental Protection Agency Pesticide Assessment Guidelines, Subdivision F, Series 81-3 Hazard Evaluation: Human and Domestic Animals, Section 81-3, which is comparable to OECD 102 and EC B.2.

GLP (self certification

by the laboratory)

Rat

Sprage-dawley

5 per sex

Nominal concentrations:

6.6, 8.1, 18.6, 23.7, and 25.9 mg/L

Analytical concentrations:

0.14, 0.58, 0.79, 0.95, and 1.4 mg/L   6.6, 8.1, 18.6, 23.7, and 25.9 mg/L        6.6, 8.1, 18.6, 23.7, and 25.9 mg/L

A combined LC50value (males + females) of 1.08 mg/L (95% confidence limits = 0.71 – 1.66 mg/L)

Mortality was seen at all of the exposure levels, with most of the deaths occurring on the first day post dose. Toxicologically significant pharmacotoxic signs, such as labored breathing, were noted at all exposure levels. Due to high mortality at the higher dose levels, body weight effects could only be assessed at the two lowest doses. Weight gain was depressed at both doses during the two-week post-exposure period. Pulmonary congestion was the most common macroscopic observation at necropsy. No gross pulmonary abnormalities were seen in animals that survived the observation period. 

Key Study

7.2.2.001

 

ESPTF6013-001

 

Drummond JG (1987)

(unpublished)

The information contained within this robust summary document comes from studies which are in the ownership of Arch Chemicals Inc. and which are protected in several regions globally. This information may not be used for any purpose other than in support of the Chemical safety Report submitted by Arch Chemicals Inc. under RegulationEC 1907/2006.

Justification for classification or non-classification