DEXAMETHASONE

Overview

Chemical Names

(11beta, 16alpha)-9-FLUORO-11,17,21-TRIHYDROXY-16-METHYLPREGNA-1,4-DIENE-3,20-DIONE

CAS number

50-02-2

Functional Class

Veterinary Drug
GLUCOCORTICOSTEROID

Evaluations

Evaluation year: 2008

ADI:
0–0.015 μg/kg body

Comments:

Based on its long history of use in human medicine and because dexamethasone was negative in genotoxicity assays, the Committee was not concerned about the carcinogenic potential of dexamethasone. An ADI of 0–0.015 μg/kg bw/d was established at the 42nd meeting, based on a NOEL of 1.5 µg/kg bw/d for the induction of tyrosine aminotransferase activity in rat liver and a 100-fold safety factor. Due to the careful selection of the dose levels in this study the Committee did not round this figure. The Committee recommended MRLs for cattle, pigs and horses, expressed as dexamethasone. Based on these MRLs, the maximum theoretical intake would be 1 µg/day per person, compatible with a maximum ADI of 0.9 µg for a 60-kg person. The Committee noted that at its forty-second meeting, it was concluded that dexamethasone is rapidly eliminated from muscle and milk and that the probability of exposure to residues from these tissues is low.

MRL Comment:

Recommended maximum residue limits (MRLs) for cattle, pigs and horse of - Kidney 1.0 (μg/kg) - Liver 2.0 (μg/kg) - Muscle 1.0 (μg/kg) - Milk 0.3 (μg/l)

Intake:

TMDI: 1 µg/day per person

Meeting:

Report:

TRS 954-JECFA 70

Addendum:

FAO Monograph 70

Toxicological study

Pivotal Study:

Short-term study in rats (Kietzman, 1991; Bette & Kietzmann, 1991): Rats (6/group) were gavaged with 0, 0.5, 1, 1.5, 2, or 4 µg dexamethasone/kg bw/day for 1 and 7 days. Five hours after the last application the rats were killed and blood and liver samples were taken. TAT activity was increased in a dose-dependent manner at 2 and 4 µg/kg bw/day and a significant decrease in serum corticosterone was seen at 4 µg/kg bw/day. The NOEL in this study was 1.5 µg/kg bw/day.

Animal Specie:

Rat

Effect:

Induction of hepatic tyrosine aminotransferase activity

NOEL:

1.5 µg/kg bw/d

Point of departure:

1.5 µg/kg bw/d

Evaluation year: 1998

ADI:

0-0.000015 mg/kg bw (1994)

MRL Comment:

In the absence of an acceptable analytical method for monitoring purposes, the Committee was unable to recommend MRLs

MRL Code:

W (1997)

Meeting:

Report:

TRS 888-JECFA 50/72

Tox Monograph:

FAS 33-JECFA 42/111 (1994)

Residues:

FAO JECFA Monographs 6(2009)/

Previous Years:

1997, TRS 879-JECFA 48/46, FNP 41/7-JECFA 43/15 (1994) ,FAS 33-JECFA 42/111(1994). 0-0.000015 (1994). TEMPORARY MRLs NOT EXTENDED. FU. W 1994, TRS 855-JECFA 43/44, FNP 41/7-JECFA 43/15, FAS 33-JECFA 42/111. 0-0.000015 (EST. JECFA 42). MRLs (TEMPORARY)(EX