Pseudoephedrine hydrochloride

Endpoint summary

Description of key information

In an acute oral toxicity study (OECD 401), the LD50 was determined to be ca. 1000 and 464 mg/kg bw for male and female rats, respectively. In an acute inhalation toxicity study (OECD 403), the LC50 was determined to be >2 mg/L. In an acute dermal toxicity study (OECD 402), the LD50 was determined to be >2000 mg/kg bw.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

464 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Additional information

One study is available each for acute toxicity over the oral, dermal, and inhalation route.

In an acute oral study (similar to OECD Guideline 401) 5 male and 5 female Wistar rats were dosed with 316, 464, 681, and 1000 mg/kg bw (BASF 1986). In the highest dose group, 3/5 males died and in the lower dose groups no mortality occurred, thus the LD50 for males was determined to be ca. 1000 mg/kg bw. In female rats no mortality occurred in the lowest dose group, but 2/5, 1/5, and 1/5 animals died in the 464, 681, and 1000 mg/kg bw dose group. A LD50 of ca. 464 mg/kg bw was therefore reported for female animals, although 50% mortality was not observed in any female dose group. Based on the clinical signs females seemed to be more sensitive compared to males: while in the 464 mg/kg bw dose group the males were only excited, the females showed dyspnea, excitation, staggering and poor general state. Nonetheless a clear LD50 could not be determined. Therefore, the dose at which 2 out of 5 females died has been selected as LD50 as a conservative approach.

In an acute inhalation study (OECD TG 403) 5 male and female Wistar rats were exposed (head-nose only) to 2 mg/L test substance for 4 hours (BASF 1987). No mortality occurred, but clinical signs like nose discharge (reddish), salivation, accelerated respiration were observed during exposition, as well as smeared fur (bloody, near head), accelerated/irregular respiration, respiratory sounds, and piloerection after exposition. All symptoms were reversible within 5 (males) and 8 (females) days. Thus, a LC50 of >2 mg/L was deduced for the route.

In an acute dermal toxicity study (similar to OECD TG 402) 5 male and 5 female Wistar rats were treated with 2000 mg/kg bw test substance for 24 h under semiocclusive conditions (BASF 1989). After the exposure period, skin was rinsed with warm water. No mortality occurred and no clinical or pathological abnormalities were observed. Distinct erythema and slight edema on day 1 and incrustation from day 1 to day 7was observed. The LD50 was determined to be >2000 mg/kg bw.

Justification for selection of acute toxicity – oral endpoint
One acute oral toxicity study is available. This study is adequate for covering this endpoint.

Justification for selection of acute toxicity – inhalation endpoint
One acute inhalation toxicity study is available. This study is adequate for covering this endpoint

Justification for selection of acute toxicity – dermal endpoint
One acute dermal toxicity study is available. This study is adequate for covering this endpoint

Justification for classification or non-classification

Based on oral LD50 in rats of 464 mg/kg bw for females and 1000 mg/kg bw for males, pseudoephedrine hydrochloride has to be classified for Acute toxicity Cat 4: H302: Harmful if swallowed in accordance with EU Classification, Labeling and Packaging of Substances and Mixtures (CLP) Regulation No. 1272/2008 and Xn R22: Harmful if swallowed in accordance with EU Directive 67/548 (DSD).

 

Based on the inhalation LC50 > 2 mg/L air (aerosol) classification for acute inhalation is not possible in accordance with EU Directive 67/548 (DSD) and EU Classification, Labeling and Packaging of Substances and Mixtures (CLP) Regulation No. 1272/2008.

 

Based on the acute dermal LD50 >2000 mg/kg bw classification for acute dermal toxicity is not warranted in accordance with EU Directive 67/548 (DSD) and EU Classification, Labeling and Packaging of Substances and Mixtures (CLP) Regulation No. 1272/2008.