RU 22974

Pivotal Study:

Acute RfD: neurotoxicity study in rats (Nemec, 1998a): Sprague-Dawley rats (n=12/sex/group) were gavaged once with deltamethrin in corn oil at a dose of 0, 5, 15, or 50 mg/kg bw and tested in a "functional observation battery" before treatment and 3 h, 7 days, and 14 days later. The rats were killed on day 15. The following effects were noted at 50 mg/kg (transient, 3-h post-dosing): Altered posture, convulsions (clonic and tonic), tremors, and alterations in biting and eyelid closure in the home cage; alterations in ease of removal from the cage, ease of handling, lachrymation, salivation, and fur appearance; increased time to first step; impaired mobility and gait, convulsions (clonic and tonic), tremors, decreased arousal, bizarre or stereotypic behaviour (writhing), and decreased rearing, grooming, and urination in the open field; in the sensory observations, altered approach, touch startle, and tail-pinch responses, olfactory orientation, forelimb and hindlimb extension, and air righting reflex; reduced forelimb and hindlimb grip strength, impaired rotorad performance, and altered hindlimb footsplay (males only); and increased group mean values for catalepsy and decreased group mean values for body temperature. Single males and females at 15 mg/kg bw showed potentially treatment-related signs when tested on day 0, including slight salivation in one male and slightly soiled fur on one female during handling and slightly impaired mobility of one male during the open field observations. The NOAEL for neurotoxicity was 5 mg/kg bw. ADI-Dog studies(Ryle et al., 1993; Goldenthal, 1980a, 1981): Beagles (n=4/sex/group (1-yr study); n=8/sex/group (2-yr study)) were administered deltamethrin powder (purity, 98.9%) in gelatin capsules at doses of 0, 1, 10, or 50 mg/kg bw/d for 1 year or in the diet at a concentration of 0, 1, 10, or 40 ppm (0, 0.025, 0.25, and 1 mg/kg bw/d) for 24 months. Clinical signs at 10 & 50 mg/kg bw/d were: chewing and scratching of the extremities, abnormal gait, tremors, liquid faeces, and locomotor impairment (unsteadiness, incoordination of hindlimb gait, and, sometimes, splaying of the limbs and/or digits). Such effects were also seen in association with body tremors and abnormal movements of the head. Food intake was reduced in all males at 50 mg/kg bw/day from the time of first dosing until week 4 and intermittently thereafter, sometimes coinciding with the occurrence of significant neurological signs. Trembling, high-stepping, unsteady gait, and splayed digits were noted at weeks 26 and 52 in a few animals at 50 mg/kg. The following changes were noted at week 52 in males only at 10 & 50 mg/kg: decreased packed cell volume, haemoglobin, albumin, calcium, and Na+ concentration (50 mg/kg only). No changes in blood chemistry were seen in treated females. The NOAELs for both studies was 1 mg/kg bw/d. ADI-rat studies (Goldenthal, 1980c; Richter & Goldenthal, 1983; Ryle, 1995): Deltamethrin was administered in the diet to Charles River CD rats (n=90/sex/group, study 1) or Crl:CD(SD)BR rats (70/sex/group, study 2) at concentrations of 0, 2, 20, or 50 mg/kg (0, 0.1, 1, or 2.5 mg/kg bw/d, study 1) for 24 months or 0, 25, 125, 500, or 800 ppm (0, 1.1, 5.4, 22, and 36 mg/kg bw/d (males) & 0, 1.5, 7.3, 30, and 47 mg/kg bw/d (females), study 2) for 104 weeks. Study 1 results: Body-weight gain was reduced in males from week 26 and in females during weeks 26, 65, and 78. Decreased serum alanine aminotransferase at 6 months was noted at the intermediate and high doses. Study 2 results: Uncoordinated movements of the limbs or abnormal gait characterized by splayed limbs was seen in most males and one female at 800 ppm and in a single male at 500 ppm during week 1. Unsteady gait was seen in most males and two females at 800 ppm and in a few males at 500 ppm, also during week 1. Thereafter, their incidence and severity declined gradually, so that by week 8 these effects were no longer apparent. Bodyweight gain of males at 500 or 800 ppm and of females at 800 ppm was decreased, largely due to the particularly small weight gain (and low food intake) in week 1. Thereafter, some recovery was noted in these groups, although the overall weight gain of males at 500 or 800 ppm remained slightly reduced throughout much of the treatment period. Increased incidence and degree of eosinophilic hepatocytes was noted in male rats at 500 and 800 ppm, and the livers of males at 125 and 800 ppm showed an increased incidence of ballooned cells. The NOAEL for both studies was 1-1.1 mg/kg bw/d.

Animal Specie:

Rat (ADI, acute RfD), dog (ADI)

NOAEL:

1 mg/kg bw/d (ADI); 5 mg/kg bw (acute RfD)

Point of departure:

1 mg/kg bw/d (ADI); 5 mg/kg bw (acute RfD)